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Acute Effects of Renin-Angiotensin System Blockade on Arterial Function in Hypertensive Patients

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Acute Effects of Renin-Angiotensin System Blockade on Arterial Function in Hypertensive Patients Journal of Human Hypertension (2007) 21, 654–663 & 2007 Nature Publishing Group All rights reserved 0950-9240/07 $30.00 www.nature.com/jhh ORIGINAL ARTICLE Acute effects of renin-angiotensin system blockade on arterial function in hypertensive patients KA Aznaouridis, KS Stamatelopoulos, EN Karatzis, AD Protogerou, CM Papamichael and JP Lekakis Vascular Laboratory, Department of Clinical Therapeutics, Athens Medical School, Alexandra Hospital, Athens, Greece The acute effects of the renin-angiotensin system (RAS) significant effect (P ¼ NS). Additionally, AIx was reduced blockers may be important in some clinical settings. To after quinapril (absolute decrease of 7.2%, Po0.01) and assess the acute impact of such drugs on arterial marginally after captopril (decrease of 4.7%, P ¼ 0.07). function, we studied the effects of captopril 25 mg, Only quinapril led to a beneficial change of FMD quinapril 20 mg and telmisartan 80 mg on 100 hyperten- (absolute increase of 2.7%, Po0.001). No treatment sive patients, according to a randomized, double-blind, was related to significant changes of peak hyperaemic placebo-controlled study. Central (aortic) blood pres- or 3-min hyperaemic FBF. In adjusted analyses, all the sure (BP) and augmentation index (AIx, a measure of favourable alterations induced by quinapril were inde- wave reflections), as well as flow-mediated dilatation pendent of potential confounding haemodynamic fac- (FMD) of the brachial artery and forearm blood flow tors. Our data show that acute RAS inhibition with (FBF) (measures of conduit and resistance artery quinapril (20 mg) may be more beneficial in terms of endothelial function, respectively), were evaluated be- arterial function and central haemodynamics compared fore and 2 h after oral drug administration. Compared to to captopril (25 mg) or telmisartan (80 mg). Further placebo, captopril and quinapril decreased central studies are needed to investigate whether these acute systolic (by 7.5 mm Hg, Po0.05 and by 12.3 mm Hg, arterial effects of quinapril are clinically significant. Po0.001) and diastolic BP (by 4.9 mm Hg, Po0.01 and Journal of Human Hypertension (2007) 21, 654–663; by 8.4 mm Hg, Po0.001), whereas telmisartan had no doi:10.1038/sj.jhh.1002211; published online 26 April 2007 Keywords: endothelium; wave reflection; ACE inhibition; central blood pressure; antihypertensive drugs Introduction fully explained by the respective BP change.8–10,12,14 However, different ACEIs may not confer a same Arterial elastic properties, central (aortic) haemody- degree of organoprotection, and this is perhaps due namics and peripheral endothelial function are to dissimilarities in their propensity to penetrate important predictors of cardiovascular risk.1–4 Im- vascular tissue and inhibit the tissue ACE.15,16 portantly, the recent Conduit Artery Function Although the notion of a class effect of ACEIs has Evaluation (CAFE´ ) study showed that a greater been proposed, this is not fully documented or decrease of central blood pressure (BP) with anti- universally accepted. On the other hand, angioten- hypertensive treatment is associated with reduced sin-II type-1 receptor blockers (ARBs) efficiently cardiovascular events, independent of peripheral BP block the interaction of both ACE- and non-ACE- changes.5 Likewise, there are data showing that the produced angiotensin-II with type-1 receptor, and reversal of endothelial dysfunction, that is present 6 7 these drugs are also characterized by organoprotec- in hypertensive patients, may benefit prognosis. tive effects.17 Drugs that block the renin-angiotensin system Beyond the established benefit of long-term anti- (RAS), such as angiotensin converting enzyme hypertensive therapy, there are no data to support (ACE) inhibitors (ACEIs), may improve cardiovas- that acute effects of drugs – including RAS blockers cular structure and function,8–13 and this effect is not – on BP and arterial function are clinically relevant in hypertensive patients. However, the acute effects Correspondence: Dr K Aznaouridis, Department of Cardiology, of RAS blockers may be important in some other Athens Medical School, Kyparissias 14, Kato Acharnes, Athens clinical settings, such as acute myocardial infarc- 13671, Greece. tion,18–20 coronary revascularization19,21 and even E-mail: [email protected] 22 Received 3 January 2007; revised 20 March 2007; accepted 21 non-cardiac surgery. Furthermore, there is evi- March 2007; published online 26 April 2007 dence that different drugs of the same class (ACEIs) Acute RAS blockade and arterial function KA Aznaouridis et al 655 may not be equally beneficial in such acute condi- trolled room at 231C. After a 20-min rest period, tions.21,23,24 Data comparing the acute vascular baseline measurements for evaluation of central effects of different RAS blockers in humans are haemodynamics (pulse-wave analysis), of endothe- limited.16,25–27 Accordingly, in the present rando- lial function of resistance and then of conduit mized, placebo-controlled, double-blind, parallel- arteries were taken in the supine position, in this design study, we investigated the acute effects of fixed order. The study of conduit vessels was different types of RAS blockade on arterial function preceded by a 15-min rest period to allow recovery in a population with impaired arterial performance, of vascular function. Then, the subjects were using a thorough approach that evaluates endothe- randomized to take either captopril 25 mg or lial function of both conductance and resistance quinapril 20 mg or telmisartan 80 mg, or placebo arteries and central (aortic) haemodynamics. For per os, together with drinking 200 ml of water. this purpose, we compared the effects of captopril, Randomization was undertaken by sealed envelopes quinapril (an ACEI with presumed high-tissue and gave rise to four groups with 25 patients each. affinity15,16) and telmisartan (an ARB possessing a Dosing was supervised. In a pilot study that unique action profile28) on subjects with essential consisted of eight patients in each treatment arm hypertension, which may be regarded as a model who underwent BP measurement every 30 min after of abnormal arterial function. Also, we sought to drug administration, we observed that the three investigate whether any observed vascular changes active drugs caused a maximal decrease of BP would be associated with respective alterations of approximately at 2 h. Therefore, vascular studies peripheral BP. were repeated 2 h after drug intake in all groups. The study protocol was approved by our Institu- tional Research Ethics Committee and all subjects Materials and methods gave informed consent. Study population We evaluated consecutive patients with mild to Evaluation of central haemodynamics (pulse-wave moderate hypertension who were referred from the analysis) Hypertension Unit to our Laboratory for vascular Central (aortic) BPs and augmentation index (AIx), studies for research purposes. A full medical history an index of wave reflections,1,3,29–31 were calculated was taken and physical examination was performed. using a validated, commercially available system Patients who had evidence of secondary hyperten- (SphygmoCor, AtCor Medical, Sydney, Australia), sion, coronary artery disease, heart failure, history of which employs the principle of applanation tono- a cerebrovascular event, endocrinopathy, or an acute metry. Waveforms of radial pressure (provided by or chronic inflammatory-infectious disease were radial artery tonometry) were calibrated according to excluded. All subjects were clinically well and sphygmomanometric SBP and DBP measured in the taking no antioxidant vitamins, anti-inflammatory brachial artery, since there is practically negligible or steroid substances. No female participant was on pressure amplification between the brachial and oral contraceptives or oestrogen replacement ther- radial arteries. Mean arterial pressure (MAP) was apy. The final study comprised 100 patients (mean then computed automatically by numerically aver- age 57.2 years, 48 males). aging of the radial pressure waveform.32 The central Brachial systolic and diastolic BP (SBP and DBP) BP was derived with the use of a generalized transfer in the sitting position were measured in the right function, which is an accurate estimate of the arm with a mercury sphygmomanometer on three central arterial pressure waveform. Augmented occasions 1 min apart, after the subjects had rested pressure (AP) is the pressure added to the incident for 15 min, and the mean value was calculated. wave by the returning reflected one and represents Hypertension was diagnosed when BP was above the pressure boost with which the left ventricle must 140/90 mm Hg in three different visits a week apart, cope at systole. AIx (defined as AP divided by pulse or if chronic use of antihypertensive drugs was pressure and expressed as a percentage) is a documented. In that case, medication was with- composite measure of the magnitude of wave drawn for 2 weeks before the study. Subjects reflections and arterial stiffness, which affects abstained from caffeine, ethanol and flavonoid- timing of wave reflections. For similar heart rate containing beverages for at least 12 h before the and effective length of the arterial system, larger study. values of AIx indicate increased wave reflections from the periphery and/or earlier return of the reflected wave as a result of increased pulse-wave Study design velocity (owing to increased arterial stiffness), and The study was carried out
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