Efficacy of Clonidine in a Patient with Refractory Hypertension and Chronic Renal Failure Exhibiting Neurovascular Compression O

CORRESPONDENCE

Efﬁcacy of clonidine in a patient with refractory hypertension and chronic renal failure exhibiting neurovascular compression of the rostral ventrolateral medulla

Hypertension Research (2009) 32, 227–228; doi:10.1038/hr.2009.1; published online 13 February 2009

To the editor: tion, 0.57 ng mlÀ1 (normal range: 0.15– part, to the increased SNA and BP. Additional The rostral ventrolateral medulla (RVLM) is 0.57 ng mlÀ1). Echocardiogram revealed left treatment with clonidine was selected instead an important center for the regulation of ventricular hypertrophy (LVH) and normal of MVD of the RVLM, as complete remission sympathetic and cardiovascular activities.1 systolic function. 131I-meta-iodobenzylguani- of hypertension could not be expected An association between neurovascular com- dine scintigraphy revealed no abnormal because of the possible existence of reno- pression (NVC) of the RVLM and essential uptakes. Magnetic resonance imaging showed parenchymal hypertension even though inva- hypertension (EH) has been suggested.2,3 NVC of the RVLM by left posterior inferior sive MVD of the RVLM was performed. Microvascular decompression (MVD) of the cerebellar artery (Figure 1). Additional treat- Additional treatment with clonidine success- RVLM decreases blood pressure (BP) in ment with 450 mg clonidine induced rapid fully reduced BP and plasma NE levels and hypertensive patients with NVC of reduction in BP associated with decreases caused a gradual reduction in serum creati- the RVLM.2 Earlier, we reported a patient in PR and plasma NE levels (0.94 and nine. Considering that strict control of BP is with EH and NVC of the RVLM who exhib- 0.39 ng mlÀ1 just before and 4 weeks after important in the treatment of chronic kidney ited normalization of BP and decreases in clonidine treatment, respectively) (Figure 2). disease,8 it is likely that successful BP reduc- sympathetic nerve activity (SNA) by MVD of Although the doses of antihypertensive drugs tion by this regimen contributed to the reno- the RVLM.4 Therefore, MVD of the RVLM were gradually reduced, BP remained low. protective effect in this case. could be a useful therapeutic strategy to Serum creatinine gradually reduced to Involvement of increased SNA is reported reduce BP in these patients. Herein, we report 3.18 mg per 100 ml in August 2007. Hemo- not only in NVC of the RVLM but also in a patient with chronic renal failure (CRF) and globin A1c was not greatly changed (ranged CRF, LVH, and administration of antidiuretic refractory hypertension with NVC of the around 6.5%) during the course. agents.Therefore,itispossiblethatthe RVLM who exhibited prominent BP decrease This case exhibited refractory hypertension, mechanism of increased SNA in this case and improved renal function with an a2 CRF and NVC of the RVLM and increased was complex. Clonidine, an a2 adrenergic adrenergic agonist, clonidine. plasma NE concentration. Increased SNA is agonist, elicits hypotensive and sympathoinhi- The patient was a 54-year-old man with observed in hypertensive patients with NVC bitory effects by action mainly on the RVLM.9 CRF and was referred to our hospital in of the RVLM.5–7 Therefore, it was anticipated It is likely that NVC of the RVLM, at least August 2005 because of refractory hyperten- that NVC of the RVLM contributed, at least in partially, contributed to increased SNA and sion. He was diagnosed with EH and diabetes mellitus in 1985, and with CRF in 2003. Ofﬁce BP was 182/100 mm Hg and pulse Anterior rate (PR) was 62 beats minÀ1 under treatment with 80 mg nifedipine controlled release, 60 mg olmesartan, 8 mg doxazosin, Right Left 10 mg carbezirol, 60 mg furosemide and 180 mg azosemide at the ﬁrst visit. Results of the initial tests were as follows: urinary protein, 551.7 mg per g Cre; blood urea nitrogen, 48 mg per 100 ml; serum creatinine, Posterior 4.15 mg per 100ml; hemoglobin A1c, 6.5%; Figure 1 Axial magnetic resonance images. The posterior inferior cerebellar artery is compressing the and plasma norepinephrine (NE) concentra- surface of the rostral ventrolateral medulla (RVLM) (arrows). Correspondence 228

Aug 2005 Oct Feb JunOct Feb Jun 2006 2007 200 160 Systolic 120 BP 80 (mmHg) 40

Blood pressure Diastolic BP 0 70 60 50

(bpm) 40

Pulse rate 30 5 4 3 100 ml) (mg per

Creatinine 2 NE (ng ml-1) 0.57 0.94 0.39 0.37

Clonidine 450 µg day-1 Nifedipine controlled release 80 mg day-1

Olmesartan 40 mg day-1 60 mg day-1 Doxazosin 8 mg day-1 Carbezirol 10 mg day-1 Furosemide 40 mg day-1 60 mg day-1 120 mg day-1 Azosemide 180 mg day-1 60 mg day-1

Figure 2 Clinical course. NE, norepinephrine.

3 3 BP in this case, because clonidine showed Koshi Ikeda , Satoshi Sawada and 4MorimotoS,SasakiS,TakedaK,FuruyaS,NaruseS, excellent efficacy in reducing elevated SNA Toshiji Iwasaka1 Matsumoto K, Higuchi T, Saito M, Nakagawa M. Decreases in blood pressure and sympathetic nerve and BP. 1 activity by microvascular decompression of the rostral This case suggests that antihypertensive Second Department of Internal Medicine, ventrolateral medulla in essential hypertension. Stroke medical treatment with sympatholytic agents Kansai Medical University, Hirakata City, 1999; 30: 1707–1710. 2 5MorimotoS,SasakiS,ItohH,NakataT, acting on the RVLM may be useful in hyper- Osaka, Japan; Department of Internal Takeda K, Nakagawa M, Furuya S, Naruse S, tensive patients with NVC of the RVLM. To Medicine, Komatsu Hospital, Fukuyama R, Fushiki S. Sympathetic activation confirm this finding, further studies in a Neyagawa City, Osaka, Japan and and contribution of genetic factors in hypertension 3 with neurovascular compression of the rostral series of similar patients are needed. Also, Department of Radiology, ventrolateral medulla. J Hypertens 1999; 17: studies examining the effects of other a2 Kansai Medical University, 1577–1582. Hirakata City, Osaka, Japan 6MakinoY,KawanoY,OkudaN,HorioT,IwashimaY, adrenergic agonists, such as guanfacine, gua- Yamada N, Takayama M, Takishita S. Autonomic func- nabentz and a-methyldopa, are required. E-mail: [email protected] tion in hypertensive patients with neurovascular com- Clinical studies examining the effects of anti- pression of the ventrolateral medulla oblongata. J Hypertens 1999; 17: 1257–1263. hypertensive agents to reduce SNA (clonidine 7 Sendeski MM, Consolim-Colombo FM, Leite CC, Ribira and the L- and N-type calcium channel MC, Lessa P, Krieger EM. Increased sympathetic nerve 1 Dampney RA, Goodchild AK, Robertson LG, Montgomery activity correlates with neurovascular compression at the blocker) in patients with hypertension are in W. Role of ventrolateral medulla in vasomotor regulation: rostral ventrolateral medulla. Hypertension 2006; 47: progress, and if the present findings are con- a correlative anatomical and physiological study. Brain 988–995. firmed, assessment of whether NVC of the Res Rev 1982; 249: 223–235. 8 Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, 2 Jannetta PJ, Segal R, Wolfson SK. Neurogenic hyper- Toro R, Tuttle K, Douglas J, Hsueh W, Sowers J. Preser- RVLM exists or not will be recommended in tension: etiology and surgical treatment. I. Observations ving renal function in adults with hypertension and patients with refractory hypertension. in 53 patients. Ann Surg 1985; 201: 391–398. diabetes: a consensus approach. Am J Kidney Dis 3 MorimotoS,SasakiS,MikiS,KawaT,ItohH,NakataT, 2000; 36: 646–661. Takeda K, Nakagawa M, Kizu O, Furuya S, Naruse S, 9 Ruffolo Jr RR, Nichols AJ, Stadel JM, Hieble JP. Phar- 1 1 Maeda T. Neurovascular compression of the rostral macologic and therapeutic applications of 2-adrenocep- Satoshi Morimoto , Yasuko Aota , ventrolateral medulla related to essential hypertension. tor subtypes. Annu Rev Pharmacol Toxicol 1993; 33: 1 2 Takao Sakuma , Akira Ichibangase , Hypertension 1997; 30 (Part 1): 77–82. 243–279.

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