DOCSLIB.ORG

Vasopressin Mechanism–Mediated Pressor Responses Caused by Central Angiotensin II in the Ovine Fetus

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Vasopressin Mechanism–Mediated Pressor Responses Caused by Central Angiotensin II in the Ovine Fetus 0031-3998/04/5605-0756 PEDIATRIC RESEARCH Vol. 56, No. 5, 2004 Copyright © 2004 International Pediatric Research Foundation, Inc. Printed in U.S.A. Vasopressin Mechanism–Mediated Pressor Responses Caused by Central Angiotensin II in the Ovine Fetus LIJUN SHI, CATALINA GUERRA, JIAMING YAO, AND ZHICE XU Harbor-UCLA Medical Center and Research and Education Institute, Torrance, CA 90502 [L.S., C.G., J.Y. Z.X.]; and Soochaw University School of Medicine, Suzhou 215007, China [Z.X.] ABSTRACT AVP not only influences renal water excretion but also has receptor antagonist had no effect on either fetal or maternal profound cardiovascular effects in adults. Our recent studies have baseline BP. However, intracerebroventricular Ang II–increased demonstrated that central angiotensin induced fetal pressor re- BP was partially inhibited, although not completely abolished, by sponses accompanied with AVP release. However, little is the V1-receptor blockade. In contrast, fetal i.v. infusion of known of hormonal mechanisms in angiotensin-mediated fetal V2-receptor antagonist had no effect on the pressor responses blood pressure (BP) changes. The present study determined AVP induced by central Ang II. The results suggest that the central mechanisms in central angiotensin-mediated fetal pressor re- Ang II–mediated pressor responses at the last third of gestation is sponses. The V1-receptor antagonist or V2-receptor antagonist mediated partially by the AVP mechanism via V1 not V2 was infused intravenously into the ovine fetus at 90% gestation. receptors. (Pediatr Res 56: 756–762, 2004) Angiotensin II (Ang II; 1.5 ␮g/kg) was then injected intracere- broventricularly into the chronically instrumented fetus. Ang II Abbreviations produced a significant increase in fetal systolic, diastolic, and A-MAP, mean arterial pressure adjusted to amniotic pressure mean arterial pressure adjusted to amniotic pressure (A-MAP). Ang II, angiotensin II The enhanced fetal A-MAP was associated with intense c-fos AVP-ir, AVP-immunoreactivity expression in the central putative cardiovascular area: the para- BP, blood pressure ventricular nuclei (PVN). Double labeling demonstrated that a FOS-ir, c-fos immunoreactivity number of the AVP-containing neurons in the PVN were ex- i.c.v., intracerebroventricular pressing c-fos in response to central Ang II. Consistent with the MAP, mean arterial pressure activation of AVP neurons in the PVN, fetal plasma AVP was PVN, paraventricular nuclei markedly enhanced. Fetal i.v. V1-receptor antagonist or V2- RAS, rennin-angiotensin system The nonapeptide AVP, also known as antidiuretic hormone, has II (Ang II), are essential in the control of cardiovascular functions. multiple actions, including water reabsorption and vasoconstric- Central renin-angiotensin system (RAS) plays an important role in tion in the periphery. This peptide also plays a role in cardiovas- the regulation of arterial pressure and in the development of cular diseases, including hypertension and congestive heart failure certain forms of clinical and experimental hypertension (3,5,6). (1). In adults, plasma AVP has been reported to be elevated in Under certain conditions, the RAS and the AVP system operate as some forms of hypertension, and this elevation correlates best reciprocal mechanisms in the control of vascular resistance and with the severity of hypertension (2). Recent findings have dem- arterial pressure in adults (7). For example, intracerebroventricular onstrated that the development of cardiovascular regulatory mech- (i.c.v.) administration of Ang II causes a rise in blood pressure anisms starts before birth and that the in utero development of (BP) associated with AVP release (8–10). The pressor response cardiovascular regulation is critical for fetal cardiovascular ho- induced by the i.c.v. Ang II in adults is partially related to an meostasis (3,4). Several peptides, including AVP and angiotensin increase of AVP. In fetuses, previous study has shown that AVP plays a role in BP regulation during periods of hypovolemia (11). Received January 13, 2004; accepted April 15, 2004. The enhanced plasma AVP contributed to a rise of mean arterial Correspondence: Zhice Xu, Ph.D., Harbor-UCLA Medical Center, 1124 West Carson pressure (MAP) and decreased heart rate. I.v. infusion of the Street, RB-1, Torrance, CA 90502; e-mail: [email protected] vasopressin V1-receptor blockade abolished the increase of the Research described in this article is supported by March of Dimes Research Grant, External Research Grant from Philip Morris USA Inc., and UCLA Faculty Grant Program fetal MAP after application of AVP (12,13). Award to Z.X. Recent studies in our laboratory have demonstrated that DOI: 10.1203/01.PDR.0000141519.85908.68 i.c.v. Ang II increased fetal arterial pressure associated with an 756 FETAL V1-RECEPTOR AND ANG-RELATED PRESSOR 757 elevation of plasma AVP in the near-term ovine fetus (14). samples were replaced with an equivalent volume of heparin- This raised a question of whether the Ang-mediated fetal ized maternal blood withdrawn before the study. pressor response was mediated by hormonal mechanisms. Study 2: effect of i.v. V1- or V2-antagonist on the pressor Therefore, the present study sought to determine the AVP response caused by central Ang II. Animals (n ϭ 5) were mechanism in Ang-induced pressor responses and determine assigned for three experimental treatments on separate days which subtype of AVP receptors may be involved. AVP is randomly. Study began with a baseline (Ϫ30 to 0 min) fol- synthesized mainly in supraoptic nuclei and paraventricular lowed by a study period (0 to 90 min) after i.c.v. Ang II (1.5 nuclei (PVN) in the hypothalamus (3). Thus, we also sought to ␮g/kg) injection into the fetus, or, after the baseline (Ϫ60 to determine the hypothalamic AVP cellular activation under the Ϫ20 min) period, either [deamino-Pen1, O-Me-Tyr2, Arg8]- condition of i.c.v. administration of Ang II in the near-term vasopressin (a potent V1-antagonist; 10 ␮g/kg; Sigma Chem- 1 2 ovine fetus. ical Co., St. Louis, MO) or [adamantaneacetyl , O-Et-D-Tyr , Val4, aminobutyryl6, Arg8,9]-vasopressin (a potent V2- antagonist; 150 ␮g/kg; Sigma Chemical Co.), dissolved in 10 METHODS mL of 0.9% NaCl saline, was infused into the fetal vein catheter for 30 min (i.e. from Ϫ20 to 10 min) by an infusion Studies were performed in chronically instrumented fetal pump, Ang II (1.5 ␮g/kg) was then injected intracerebroven- sheep at 90% of gestation. Animals were housed indoors in tricularly into the fetus at 0 min. The doses of the drugs were individual steel study cages and were acclimated to a 12:12-h referred to in previous reports (16–18). Blood samples (4 mL light-dark cycle. Water and food (alfalfa pellets) were provided each) were withdrawn from the fetal and maternal arterial ad libitum. All surgical and experimental procedures have been catheters at Ϫ30, Ϫ10, 0, 10, 25, 40, and 60 min for measure- approved by the Animal Care Committee. ments of blood gases, hematocrit, plasma osmolality, plasma Surgical preparation. For the surgical procedures, ketamine electrolytes, and AVP. hydrochloride (20 mg/kg, i.m.) was injected in ewes. Anesthe- Throughout studies, maternal/fetal systolic and diastolic sia was maintained with 3% isoflurane and 1 L/min oxygen. pressure, heart rate, and amniotic pressure were recorded con- The uterus was opened over the fetal hindlimbs, and polyeth- tinuously. The fetal MAP was corrected against amniotic fluid ylene catheters were placed in the maternal (inner diameter: 1.8 pressure. Fetal and maternal BP was measured by means of a mm; outer diameter: 2.3 mm) and fetal (inner diameter: 1.0 Beckman R612 (Beckman Instruments, Fullerton, CA) physi- mm; outer diameter: 1.8 mm) femoral vein and artery. An ologic recorder with Statham (Garret, Oxnard, CA) P23 trans- intrauterine catheter was inserted for measuring amniotic fluid ducers. BP and heart rate were determined by computer anal- pressure. An intracranial catheter was placed in one of the fetal ysis of waveforms using a customized pattern recognition lateral ventricles and held in place with dental cement as algorithm. reported (15). Patency of the catheter at insertion was assessed Arterial blood values and AVP analysis. Arterial pH, blood by free flow of cerebrospinal fluid via gravity drainage. The gases (PO2,PCO2), and Hb were measured with a Radiometer placement of cannulae was finally verified with histologic BM 33 MK2-PHM 72 MKS acid-base analyzer system (Radi- analysis. The fetus was then returned to the uterus, and the ometer, Copenhagen, Denmark). Plasma osmolality was mea- uterus was closed using a double row of sutures. All catheters sured on an Advanced Digimatic osmometer (Advanced In- were led to the ewe’s flank. The ends of the catheters were held struments, Needham Heights, MA). Plasma Naϩ,Kϩ, and ClϪ in place in a small cloth pocket sutured to the skin of the ewe. concentrations were determined by a Nova analyzer (Nova During the initial 2 d of recovery, gentamicin (8 mg) and Biomedical, Waltham, MA). oxacillin (33 mg) were administered intravenously to the fetus, The blood samples were collected into iced tubes that con- and gentamicin (72 mg), oxacillin (1g), and chloramphenicol tained lithium heparin and centrifuged immediately for AVP (1 g) were administered intravenously to the ewe (15). All RIA. Plasma AVP concentrations were measured using Sep- animals were allowed 5 d for postoperative recovery. Pak C18 cartridge (Waters Associates, Milford, MA) extrac- Experimental protocol. On the testing day, sheep were tion (19). Sensitivity of the AVP antiserum is 1.5 pg/tube with allowed 60–100 min to acclimatize to the testing room. When intra-assay and interassay coefficients of variation of 6 and 8%, maternal and fetal heart rates and arterial pressures seemed to respectively. AVP recoveries average 70% in our experiments.
Load more

Recommended publications
  • Actions of Vasoactive Intestinal Peptide on the Rat Adrenal Zona Glomerulosa
    51 Actions of vasoactive intestinal peptide on the rat adrenal zona glomerulosa J P Hinson, J R Puddefoot and S Kapas1 Molecular and Cellular Biology Section, Division of Biomedical Sciences, St Bartholomew’s and The Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, Mile End Road, London E1 4NS, UK 1Oral Diseases Research Centre, St Bartholomew’s and The Royal London School of Medicine and Dentistry, 2 Newark Street, London E1 2AT, UK (Requests for offprints should be addressed to J P Hinson) Abstract Previous studies, by this group and others, have shown that The response to VIP in adrenals obtained from rats fed vasoactive intestinal peptide (VIP) stimulates aldosterone a low sodium diet was also investigated. Previous studies secretion, and that the actions of VIP on aldosterone have found that adrenals from animals on a low sodium secretion by the rat adrenal cortex are blocked by â diet exhibit increased responsiveness to VIP. Specific VIP adrenergic antagonists, suggesting that VIP may act by binding sites were identified, although the concentration the local release of catecholamines. The present studies or affinity of binding sites in the low sodium group was not were designed to test this hypothesis further, by measur- significantly different from the controls. In the low sodium ing catecholamine release by adrenal capsular tissue in group VIP was found to increase catecholamine release to response to VIP stimulation. the same extent as in the control group, however, in Using intact capsular tissue it was found that VIP caused contrast to the control group, the adrenal response to VIP a dose-dependent increase in aldosterone secretion, with a was not altered by adrenergic antagonists in the low concomitant increase in both adrenaline and noradrenaline sodium group.
    [Show full text]
  • Angiotensin II Protocol
    Angiotensin II (Giapreza ™) Protocol Background Sepsis and septic shock are medical emergencies that affect millions of people each year and killing as many as 1 in 4.1 The cornerstones of therapy are fluid resuscitation, early appropriate antibiotics, source control if needed and vasopressors. A small portion of patients fail to respond to these therapies and develop refractory shock. The definition of refractory septic shock varies in the literature but is generally considered to be hypotension, with end-organ dysfunction, requiring high-dose vasopressor support.2 The associated mortality of refractory septic shock is up to 60% and as high as 80-90% in patients requiring more than 1 mcg/kg/min of norepinephrine.2,3 Patients who develop refractory septic shock comprise a very small portion of the population in large randomized controlled trials therefore limited data is available regarding outcomes and management. Indications: Angiotensin II (Ang II) is a vasoconstrictor used to increase blood pressure in adults with septic or other distributive shock. Administration: Starting dose of 5 (nanograms) ng/kg/min intravenously via central line only. Titration: Every 5 minutes by increments of 5 ng/kg/min as needed. Maximum dose should not exceed 80 ng/kg/min (During the first 3 hours of administration); after the first 3 hours the maintenance (maximum) dose is 40 ng/kg/min. Monitoring: Critical care setting only with telemetry, arterial blood pressure, and continuous SpO2 monitoring. DVT Prophylaxis should be started (unless contraindicated)
    [Show full text]
  • Pulmonary Clearance of Vasoactive Intestinal Peptide
    Thorax: first published as 10.1136/thx.41.2.88 on 1 February 1986. Downloaded from Thorax 1986;41:88-93 Pulmonary clearance of vasoactive intestinal peptide MICHAEL P BARROWCLIFFE, ALYN MORICE, J GARETH JONES, PETER S SEVER From the Division ofAnaesthesia, Clinical Research Centre, Harrow, and the Department ofClinical Pharmacology and Therapeutics, St Mary's Hospital Medical School, London ABSTRACT Vasoactive intestinal peptide causes bronchodilatation when given intravenously but is less effective in both animals and man when given by inhalation. This difference may be due to poor transit of the peptide across the bronchial epithelium. To test this hypothesis pulmonary clearance of radiolabelled vasoactive intestinal peptide was measured in Sprague Dawley rats and compared with that of pertechnetate (Tc04 ) and diethylene triamine pentaacetate (DTPA). Despite a mole- cular weight (MW) of 3450, iodinated vasoactive intestinal peptide was cleared rapidly from the lungs, with a mean half time (t /2) of 19 minutes after an initial slower phase. This compares with a t'/2 of 10 minutes with Tc04 (MW 163) and a t1/2 of 158 minutes with DTPA (MW 492). The possibility that vasoactive intestinal peptide mediates a non-specific increase in permeability was discounted by the fact that the combination ofvasoactive intestinal peptide and DTPA did not alter DTPA clearance significantly. Chromatography and radioimmunoassay of blood taken after intra- tracheal administration of vasoactive intestinal peptide demonstrated a metabolite but no un- changed peptide. An intravenous injection ofthe peptide disappeared on first pass through the lung. copyright. It is concluded that inhaled vasoactive intestinal peptide lacks efficacy as a bronchodilator not because of slow diffusion to airway smooth muscle but because it is metabolised at an early stage of its passage through the respiratory epithelium.
    [Show full text]
  • Role of the Renin-Angiotensin-Aldosterone
    International Journal of Molecular Sciences Review Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension Natalia Muñoz-Durango 1,†, Cristóbal A. Fuentes 2,†, Andrés E. Castillo 2, Luis Martín González-Gómez 2, Andrea Vecchiola 2, Carlos E. Fardella 2,* and Alexis M. Kalergis 1,2,* 1 Millenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330025 Santiago, Chile; [email protected] 2 Millenium Institute on Immunology and Immunotherapy, Departamento de Endocrinología, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8330074 Santiago, Chile; [email protected] (C.A.F.); [email protected] (A.E.C.); [email protected] (L.M.G.-G.); [email protected] (A.V.) * Correspondence: [email protected] (C.E.F.); [email protected] (A.M.K.); Tel.: +56-223-543-813 (C.E.F.); +56-223-542-842 (A.M.K.) † These authors contributed equally in this manuscript. Academic Editor: Anastasia Susie Mihailidou Received: 24 March 2016; Accepted: 10 May 2016; Published: 23 June 2016 Abstract: Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition.
    [Show full text]
  • Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD
    International Journal of Molecular Sciences Review Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD Anastasia V. Poznyak 1,* , Dwaipayan Bharadwaj 2,3, Gauri Prasad 3, Andrey V. Grechko 4, Margarita A. Sazonova 5 and Alexander N. Orekhov 1,5,6,* 1 Institute for Atherosclerosis Research, Skolkovo Innovative Center, 121609 Moscow, Russia 2 Academy of Scientific and Innovative Research, CSIR-Institute of Genomics and Integrative Biology Campus, New Delhi 110067, India; [email protected] 3 Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India; [email protected] 4 Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 14-3 Solyanka Street, 109240 Moscow, Russia; [email protected] 5 Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia; [email protected] 6 Institute of Human Morphology, 3 Tsyurupa Street, 117418 Moscow, Russia * Correspondence: [email protected] (A.V.P.); [email protected] (A.N.O.) Abstract: Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury. There are no effective treatment options, as well as preventive measures for atherosclerosis. However, this disease has various severe complications, the most severe of which is cardiovascular disease (CVD). It is important to note, that CVD is among the leading causes of death worldwide. The renin–angiotensin–aldosterone system (RAAS) is an important part of inflammatory response regulation. This system contributes to Citation: Poznyak, A.V.; Bharadwaj, the recruitment of inflammatory cells to the injured site and stimulates the production of various D.; Prasad, G.; Grechko, A.V.; cytokines, such as IL-6, TNF-a, and COX-2.
    [Show full text]
  • Five Decades of Research on Opioid Peptides: Current Knowledge and Unanswered Questions
    Molecular Pharmacology Fast Forward. Published on June 2, 2020 as DOI: 10.1124/mol.120.119388 This article has not been copyedited and formatted. The final version may differ from this version. File name: Opioid peptides v45 Date: 5/28/20 Review for Mol Pharm Special Issue celebrating 50 years of INRC Five decades of research on opioid peptides: Current knowledge and unanswered questions Lloyd D. Fricker1, Elyssa B. Margolis2, Ivone Gomes3, Lakshmi A. Devi3 1Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; E-mail: [email protected] 2Department of Neurology, UCSF Weill Institute for Neurosciences, 675 Nelson Rising Lane, San Francisco, CA 94143, USA; E-mail: [email protected] 3Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, Annenberg Downloaded from Building, One Gustave L. Levy Place, New York, NY 10029, USA; E-mail: [email protected] Running Title: Opioid peptides molpharm.aspetjournals.org Contact info for corresponding author(s): Lloyd Fricker, Ph.D. Department of Molecular Pharmacology Albert Einstein College of Medicine 1300 Morris Park Ave Bronx, NY 10461 Office: 718-430-4225 FAX: 718-430-8922 at ASPET Journals on October 1, 2021 Email: [email protected] Footnotes: The writing of the manuscript was funded in part by NIH grants DA008863 and NS026880 (to LAD) and AA026609 (to EBM). List of nonstandard abbreviations: ACTH Adrenocorticotrophic hormone AgRP Agouti-related peptide (AgRP) α-MSH Alpha-melanocyte stimulating hormone CART Cocaine- and amphetamine-regulated transcript CLIP Corticotropin-like intermediate lobe peptide DAMGO D-Ala2, N-MePhe4, Gly-ol]-enkephalin DOR Delta opioid receptor DPDPE [D-Pen2,D- Pen5]-enkephalin KOR Kappa opioid receptor MOR Mu opioid receptor PDYN Prodynorphin PENK Proenkephalin PET Positron-emission tomography PNOC Pronociceptin POMC Proopiomelanocortin 1 Molecular Pharmacology Fast Forward.
    [Show full text]
  • The Role of Corticotropin-Releasing Hormone at Peripheral Nociceptors: Implications for Pain Modulation
    biomedicines Review The Role of Corticotropin-Releasing Hormone at Peripheral Nociceptors: Implications for Pain Modulation Haiyan Zheng 1, Ji Yeon Lim 1, Jae Young Seong 1 and Sun Wook Hwang 1,2,* 1 Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea; [email protected] (H.Z.); [email protected] (J.Y.L.); [email protected] (J.Y.S.) 2 Department of Physiology, College of Medicine, Korea University, Seoul 02841, Korea * Correspondence: [email protected]; Tel.: +82-2-2286-1204; Fax: +82-2-925-5492 Received: 12 November 2020; Accepted: 15 December 2020; Published: 17 December 2020 Abstract: Peripheral nociceptors and their synaptic partners utilize neuropeptides for signal transmission. Such communication tunes the excitatory and inhibitory function of nociceptor-based circuits, eventually contributing to pain modulation. Corticotropin-releasing hormone (CRH) is the initiator hormone for the conventional hypothalamic-pituitary-adrenal axis, preparing our body for stress insults. Although knowledge of the expression and functional profiles of CRH and its receptors and the outcomes of their interactions has been actively accumulating for many brain regions, those for nociceptors are still under gradual investigation. Currently, based on the evidence of their expressions in nociceptors and their neighboring components, several hypotheses for possible pain modulations are emerging. Here we overview the historical attention to CRH and its receptors on the peripheral nociception and the recent increases in information regarding their roles in tuning pain signals. We also briefly contemplate the possibility that the stress-response paradigm can be locally intrapolated into intercellular communication that is driven by nociceptor neurons.
    [Show full text]
  • Secretion, Degradation, and Elimination of Glucagon-Like
    Secretion, Degradation, and Elimination of Glucagon-Like Peptide 1 and Gastric Inhibitory Polypeptide in Patients with Chronic Renal Insufficiency and Healthy Control Subjects Juris J. Meier,1 Michael A. Nauck,1,2 Daniel Kranz,1 Jens J. Holst,3 Carolyn F. Deacon,3 Dirk Gaeckler,4 Wolfgang E. Schmidt,1 and Baptist Gallwitz1 CRI patients vs. healthy control subjects, respectively. ؎ ؎ Glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important factors in the patho- Plasma half-lives of intact GIP were 6.9 1.4 and 5.0 ؎ ؎ ؍ genesis of type 2 diabetes and have a promising thera- 1.2 min (P 0.31) and 38.1 6.0 and 22.4 3.0 min for ؍ peutic potential. Alterations of their secretion, in vivo the GIP metabolite (P 0.032) for CRI patients vs. degradation, and elimination in patients with chronic healthy control subjects, respectively. Insulin concen- renal insufficiency (CRI) have not yet been character- trations tended to be lower in the patients during all ized. Ten patients with CRI (aged 47 ؎ 15 years, BMI experiments, whereas C-peptide levels tended to be kg/m2, and serum creatinine 2.18 ؎ 0.86 elevated. These data underline the importance of the 2.2 ؎ 24.5 mg/dl) and 10 matched healthy control subjects (aged kidneys for the final elimination of GIP and GLP-1. The years, BMI 24.9 ؎ 3.4 kg/m2, and serum creati- initial dipeptidyl peptidase IV–mediated degradation of 12 ؎ 44 nine 0.89 ؎ 0.10 mg/dl) were included. On separate both hormones is almost unaffected by impairments in occasions, an oral glucose tolerance test (75 g), an renal function.
    [Show full text]
  • Renin-Angiotensin-Aldosterone System (RAAS) and Hypothalamic-Pituitary
    Renin-Angiotensin-Aldosterone System (RAAS) and Hypothalamic-Pituitary- Adrenal Axis (HPAA) in Critically Ill Foals THESIS Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Katarzyna Agnieszka Dembek Graduate Program in Veterinary Clinical Sciences The Ohio State University 2012 Master's Examination Committee: Associate Professor Ramiro Toribio; Advisor Professor Catherine Kohn Assistant Professor Samuel Hurcombe Copyrighted by Katarzyna Agnieszka Dembek 2012 Abstract Sepsis is a major cause of morbidity and mortality in neonatal foals. Dysfunction of the hypothalamic-pituitary-adrenal axis (HPAA), manifested as relative adrenal insufficiency (RAI), has been associated with sepsis in newborn foals. Information on the renin- angiotensin-aldosterone system (RAAS) is minimal in healthy or sick foals. The HPAA and RAAS are interactive systems, and a relationship between RAAS activation and RAI is well documented in critically ill children, but limited information exists in septic foals. We hypothesized that in critically ill septic newborn foals the RAAS and HPAA will be activated by systemic inflammation and hypoperfusion and the degree of activation will be associated with severity of sepsis and mortality. For this project, 167 (study 1) and 182 (study 2) sick and healthy foals of less than 7 days of age were included. Blood samples were collected on admission from septic (sepsis score >12), sick non-septic (SNS), and healthy foals. Blood concentrations of cortisol, aldosterone, angiotensin-II (ANG-II), corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), adrenocorticotropic hormone (ACTH) and plasma renin activity were determined by immunoassays. Aldosterone, ANG-II, ACTH and cortisol concentrations were higher in septic compared to healthy foals (P<0.05).
    [Show full text]
  • Bioactive Angiotensin Peptides
    Journal of Human Hypertension (1998) 12, 289–293 1998 Stockton Press. All rights reserved 0950-9240/98 $12.00 Bioactive angiotensin peptides I Moeller, AM Allen, S-Y Chai, J Zhuo and FAO Mendelsohn The Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria 3052, Australia Angiotensin II is recognised as the principle active pep- involved in memory retention and neuronal develop- tide of the renin-angiotensin system, exerting effects on ment. Furthermore, our demonstration that a globin fluid and electrolyte homeostasis, and cardiovascular fragment, LVV-haemorphin-7, binds with high affinity to control including neural and long term trophic effects. the angiotensin IV binding site and is abundant in the However, recent studies indicate that other angiotensin brain, indicates that this may represent a novel brain peptides such as angiotensin III, angiotensin II (1–7) and neuropeptide system. It now appears, that the renin- angiotensin IV, may have specific actions. Interestingly, angiotensin system is more complex than previously recent work involving angiotensin IV demonstrates that thought and capable of generating multiple, active pep- this peptide binds to specific receptors and may be tides which elicit numerous diverse actions. Keywords: angiotensin metabolites; angiotensin III; angiotensin II(1–7); angiotensin IV; globin Bioactive angiotensin peptides tropic and chronotropic effects and facilitates sympathetic activity.13 The renin-angiotensin system (RAS) was initially Acting on the brain, Ang II induces fluid and salt identified as a circulating humoral system with the ingestion, modulates neuroendocrine systems, effector peptide, angiotensin II (Ang II), generated including vasopressin and corticotropin releasing by an enzymatic cascade.
    [Show full text]
  • Organ, and Pituitary Gland of Hypophysectomized
    Proc. Nati. Acad. Sci. USA Vol. 86, pp. 725-729, January 1989 Neurobiology Angiotensin II receptors in paraventricular nucleus, subfornical organ, and pituitary gland of hypophysectomized, adrenalectomized, and vasopressin-deficient rats (receptor autoradiography/corticotropin-releasing hormone/adrenocorticotropin/blood pressure regulation/Brattleboro rats) EERO CASTRIN AND JUAN M. SAAVEDRA Unit of Preclinical Neuropharmacology, Laboratory of Clinical Science, National Institute of Mental Health, Building 10, Room 2D45, 9000 Rockville Pike, Bethesda, MD 20892 Communicated by Irvine H. Page, October 18, 1988 (receivedfor review August 10, 1988) ABSTRACT Angiotensin II has been implicated in the receptors in circumventricular organs and stimulate the brain regulation of adrenocorticotropin and vasopressin secretion. angiotensin II system, which leads to increased ACTH Angiotensin II may influence the secretion of these hormones release probably through the stimulation of corticotropin- either directly at the pituitary gland or by increasing corti- releasing hormone (CRH) secretion from the hypothalamus cotropin-releasing hormone or vasopressin release from cells (9, 12). that are located in the paraventricular hypothalamic nucleus. The paraventricular nucleus is one ofthe key hypothalamic Pituitary hormone release may also be influenced by circulating nuclei in the neuroendocrine regulation (13). It is divided into angiotensin H through receptors outside the blood-brain distinct, biochemically specific subnuclei (13). Neurons in barrier in the subfornical organ. We have used alterations in the magnocellular subdivision, together with those in the angiotensin II receptors in hypophysectomized, adrenalecto- supraoptic nucleus, produce vasopressin and oxytocin and mized, and vasopressin-deficient Brattleboro rats as indicators project to the posterior pituitary gland, from where the of the activity of angiotensin II in the regulation of adrenocor- hormones are released to the circulation (13).
    [Show full text]
  • Gonadotropin Stimulates Ovarian Renin-Angiotensin System in the Rabbit
    Gonadotropin stimulates ovarian renin-angiotensin system in the rabbit. Y Yoshimura, … , M Jinno, Y Nakamura J Clin Invest. 1994;93(1):180-187. https://doi.org/10.1172/JCI116943. Research Article The present study was undertaken to assess the role of ovarian renin-angiotensin system (RAS) in the preovulatory cascade induced by gonadotropin exposure. In the in vitro perfused rabbit ovaries, exposure to human chorionic gonadotropin (hCG) enhanced the secretion rate of angiotensin II (Ang II) within 1 h. The secretion rate reached maximal levels at 6 h and then declined thereafter. The intrafollicular Ang II content and renin-like activity were also significantly increased at 2 and 4 h after exposure to hCG, compared with control ovaries perfused with medium alone. The level of intrafollicular Ang II after hCG exposure significantly exceeded the concentration of Ang II in an equivalent volume of plasma. The addition of 1 microM captopril to the perfusate significantly inhibited the secretion rate of Ang II stimulated by hCG; however, captopril affected neither the ovulatory efficiency nor prostaglandin production in ovaries treated with hCG. Captopril significantly inhibited the resumption of meiosis in the ovulated ova and follicular oocytes stimulated by hCG. The administration of 100 micrograms Ang II at 2-h intervals to the perfusate reversed the inhibitory effects of captopril on hCG-induced oocyte maturation. In conclusion, these data indicate that gonadotropin stimulates renin-like activity and Ang II production in the rabbit ovary.
    [Show full text]