cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2011-6-35-41cardiovascular-1961Research ArticleАРТЕРИАЛЬНАЯ ГИПЕРТОНИЯARTERIAL HYPERTENSIONОстрые сосудистые эффекты блокатора рецепторов к ангиотензину II олмесартана у здоровых лиц с нормальным уровнем артериального давления: влияние на ренин-альдостероновую системуAcute vascular effects of the angiotensin II receptor antagonist olmesartan in normal subjects: relation to the renin-aldosterone systemРезникЛ. М.ResnickL. M.КатанзароД.CatanzaroD.СеалейЖ. Е.SealeyJ. E.ЛарагДж. Х.LaraghJ. H.Центр артериальной гипертензии и сердечно-сосудистых заболеваний, отделение патофизиологии, Университет Корелла, Вейл медицинский КолледжHypertension and Cardiovascular Centers, the Division of Cardiovascular Pathophysiology, Cornell University Weill College of Medicine2011201220111063541Copyright © Резник Л.М., Катанзаро Д., Сеалей Ж.Е., Лараг Д.Х., 20112011Резник Л.М., Катанзаро Д., Сеалей Ж.Е., Лараг Д.Х.Resnick L.M., Catanzaro D., Sealey J.E., Laragh J.H.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/1961

Связь между клиническими эффектами блокаторов рецепторов к ангиотензину (БРА) и активностью рениновой системы недостаточно изучена. В исследовании у 12 лиц с нормальными уровнями артериального давления (АД) и без сопутствующей медикаментозной терапии измерялось АД, определялись показатели податливости артерий крупного (C1) и мелкого калибра (C2), общего периферического сосудистого сопротивления (ОПСС), активности ренина плазмы (АРП), а также суточной экскреции натрия (ЭNa) и альдостерона с мочой. Показатели определялись исходно и через 1, 2, 4 и 24 ч после однократного приема плацебо либо 5, 20 или 40 мг БРА олмесартана медоксомила. Исходные уровни ОПСС были обратно связаны с показателями ЭNa (r=-0,3; р=0,04). Чем выше был уровень ЭNa, тем более выраженной была вазодилатация. Оба параметра податливости сосудистой стенки были обратно связаны с исходным уровнем АРП (r=-0,32; р=0,03 для C1; r=-0,35; р=0,02 для C2). АРП служила предиктором динамики С1 (r=0,43; р=0,004) и C2 (r=0,33; р=0,04) после приема олмесартана. Чем выше была исходная АРП, тем ниже были значения C1 и С2, и тем более выраженной была положительная динамика параметров сосудистой податливости после приема олмесартана. По результатам многофакторного дисперсионного анализа, после приема олмесартана отмечалось достоверно более выраженное снижение исходных уровней систолического и диастолического АД (САД и ДАД) (р=0,003 и р<0,0001, соответственно), по сравнению с плацебо. Исходные уровни АРП были связаны со степенью снижения АД после приема олмесартана (r=-0,414; р=0,012 для САД; r=-0,561; р<0,0001 для ДАД). В частности, чем выше была исходная АРП, тем более выраженным был антигипертензивный эффект олмесартана. Большему снижению АД соответствовало более выраженное ответное повышение АРП (r=-0,44; р=0,007). Наконец, по сравнению с приемом плацебо, прием каждой из доз олмесартана сопровождался достоверным (р=0,05) уменьшением экскреции альдостерона. Во-первых, обратная связь между ЭNa и ОПСС отражает роль взаимодействия объемных и вазоконстрикторных факторов в поддержании нормального уровня АД. Во-вторых, АРП следует рассматривать в качестве физиологической детерминанты податливости артериальной стенки у лиц с нормальным АД и ответа на прием БРА олмесартана. Оценка уровней АРП может быть использована для прогноза индивидуальной клинической реакции на прием БРА.

The extent to which the clinical effects of angiotensin receptor blockers (ARB) are related to ambient renin system activity remains poorly defined. Therefore, we measured blood pressure (BP), large (C1) and small (C2) arterial compliance, systemic vascular resistance (SVR), plasma renin activity (PRA), and the 24-h urinary excretion of sodium (UNaV) and aldosterone before and 1, 2, 4, and 24 h after administration of single doses of placebo, and 5, 20, and 40 mg of the ARB olmesartan medoxomil to 12 unmedicated normotensive subjects. In the basal state, SVR was inversely related to UNaV (r=-0,3, p=0,04); the greater the UNaV, the more vasodilated the subject. Indices of arterial compliance, both C1 (r=-0,32, p=0,03) and C2 (r=-0,35, p=0,02) were inversely related to the basal PRA. Renin also predicted olmesartan-induced changes in C1 (r=0,43, p=0,004) and C2 r=0,33, p=0,04). The greater the basal PRA, the less the arterial compliance, and the more compliance improved after olmesartan. Both systolic (p=0,003) and diastolic (p<0,0001) BP fell significantly on olmesartan compared with placebo (MANOVA with time), and relations were observed between the basal PRA and olmesartan-induced changes in pressure (systolic BP: r=-0,414, p=0,012; diastolic BP: r=-0.561, p<0,0001) — the greater the initial PRA, the more olmesartan lowered BP. Furthermore, the more pressure fell, the more PRA rose reciprocally (r=-0,44, p=0,007). Finally, aldosterone excretion fell (sig=0,05) on each dose of olmesartan compared with placebo. We conclude that 1) the inverse relation of UNaV and SVR illustrates the reciprocal role of volume versus constrictor factors in maintaining normal BP; and 2) PRA is a physiologic determinant of arterial compliance in normal individuals and of the response to the ARB olmesartan. Measurement of PRA may help to predict clinical ARB responses in individual subjects.

активность ренина плазмыподатливость артериальной стенкиальдостеронроль объемных и вазоконстрикторных факторов в регуляции артериального давленияplasma renin activityarterial compliancealdosteronevolume-vasoconstriction analysis of blood pressureReferencesResnick LM Why we can’t translate clinical trials into clinical practice. Am J Hypertension 2003; 16: 421-5.Resnick LM Why we can’t translate clinical trials into clinical practice. Am J Hypertension 2003; 16: 421-5.Laragh JR Vasoconstriction-volume analysis for understanding and treating hypertension: the use of renin and aldosterone profiles. Am J Med 1973; 55: 261-74.Laragh JR Vasoconstriction-volume analysis for understanding and treating hypertension: the use of renin and aldosterone profiles. Am J Med 1973; 55: 261-74.Buhler FR, Laragh JR, Beer L, Vaughan ED Jr HRB: Propranolol inhibition of renin secretion: a specific approach to diagnosis and treatment of renin-dependent hypertensive diseases. N Engl J Med 1972; 287: 1209-13.Buhler FR, Laragh JR, Beer L, Vaughan ED Jr HRB: Propranolol inhibition of renin secretion: a specific approach to diagnosis and treatment of renin-dependent hypertensive diseases. N Engl J Med 1972; 287: 1209-13.Case DB, Wallace JM, Keim HJ, et al. Possible role of renin in hypertension as suggested by renin-sodium profiling and inhibition of converting enzyme. N Eng J Moo 1977; 296: 641;46.Case DB, Wallace JM, Keim HJ, et al. Possible role of renin in hypertension as suggested by renin-sodium profiling and inhibition of converting enzyme. N Eng J Moo 1977; 296: 641;46.Hiraohl MM, Binder M, Bur A, et al. Impact of the renin-angiotensin-aldosterone system on blood pressure response to intravenous enalaprilat in patients with hypertensive crises. J Hum Hypertens 1997; 11: 177-83.Hiraohl MM, Binder M, Bur A, et al. Impact of the renin-angiotensin-aldosterone system on blood pressure response to intravenous enalaprilat in patients with hypertensive crises. J Hum Hypertens 1997; 11: 177-83.Vaughan ED Jr, Laragh JR, Gavras I, et al. Volume factor in low and normal renin essential hypertension. Treatment with either spironolactone or chlorthalidone. Am J CardioI 1973; 32: 523-31.Vaughan ED Jr, Laragh JR, Gavras I, et al. Volume factor in low and normal renin essential hypertension. Treatment with either spironolactone or chlorthalidone. Am J CardioI 1973; 32: 523-31.Buhler FR, HuIthen UL, Kiowski W, Bolli P. Greater antihypertensive efficacy ofthe calcium channel inhibitor verapamil in older and low renin patients. C1in Sci 1982; 63: 439-42.Buhler FR, HuIthen UL, Kiowski W, Bolli P. Greater antihypertensive efficacy ofthe calcium channel inhibitor verapamil in older and low renin patients. C1in Sci 1982; 63: 439-42.Resnick L, Nicholson J, Laragh J. Calcium, the renin-angiotensin system, and the hypotensive response to nifedipine. Hypertension 1987; 10: 254-8.Resnick L, Nicholson J, Laragh J. Calcium, the renin-angiotensin system, and the hypotensive response to nifedipine. Hypertension 1987; 10: 254-8.Laragh JR, Resnick LM. Recognizing and treating two types of long-term vasoconstriction in hypertension. Kid Int 1998; 34(suppl 25): SI62-74.Laragh JR, Resnick LM. Recognizing and treating two types of long-term vasoconstriction in hypertension. Kid Int 1998; 34(suppl 25): SI62-74.Lindholm LH, Ibsen H, Dahlof B, et al. Cardiovascular morbidity and mortality with diabetes in the Losartan Intervention of Endpoint reduction in hypertension study AJH-March 2004-VOL. 17, NO.3 (LIFE): a randomised trial against atenolol. Lancet 2002: 1004-110.Lindholm LH, Ibsen H, Dahlof B, et al. Cardiovascular morbidity and mortality with diabetes in the Losartan Intervention of Endpoint reduction in hypertension study AJH-March 2004-VOL. 17, NO.3 (LIFE): a randomised trial against atenolol. Lancet 2002: 1004-110.Brunner HR, Gavras H: Angiotensin blockade for hypertension: a promise fulfilled. Lancet 2002; 359: 990-2.Brunner HR, Gavras H: Angiotensin blockade for hypertension: a promise fulfilled. Lancet 2002; 359: 990-2.Sealey IE. Plasma renin activity and plasma prorenin assay. Clio Chem 1991; 37:1811-9.Sealey IE. Plasma renin activity and plasma prorenin assay. Clio Chem 1991; 37:1811-9.Resnick LM, Militianu D, Cunnings AJ, et al. Pulse waveform analysis of arterial compliance: relation to other techniques, age, and metabolic variables. Am J Hypertens 2000; 13: 1243-9.Resnick LM, Militianu D, Cunnings AJ, et al. Pulse waveform analysis of arterial compliance: relation to other techniques, age, and metabolic variables. Am J Hypertens 2000; 13: 1243-9.Sullivan JM, Ratts TE. Hemodynamic mechanisms of adaptation to chronic high sodium intake in normal humans. Hypertension 1983; 5: 814-20.Sullivan JM, Ratts TE. Hemodynamic mechanisms of adaptation to chronic high sodium intake in normal humans. Hypertension 1983; 5: 814-20.Laragh JH, Angers M, Kel1y WG, Lieberman S. Hypotensive agents and pressor substances. The effect of epinephrine, norepinephrine, angiotensin II and others on the secretory rate ofaldosterone in man. JAMA 1960; 174: 234-40.Laragh JH, Angers M, Kel1y WG, Lieberman S. Hypotensive agents and pressor substances. The effect of epinephrine, norepinephrine, angiotensin II and others on the secretory rate ofaldosterone in man. JAMA 1960; 174: 234-40.Atlas SA, Case DB, Sealey IE, et al. Interruption of the renin-angiotensin system in hypertensive patients by captopril induces sustained reduction in aldosterone secretion, potassium retention, and natriuresis. Hypertension 1979; 1: 274-80.Atlas SA, Case DB, Sealey IE, et al. Interruption of the renin-angiotensin system in hypertensive patients by captopril induces sustained reduction in aldosterone secretion, potassium retention, and natriuresis. Hypertension 1979; 1: 274-80.Kirkendall WM, Connor WE, Abboud F, et al. The effect of dietary sodium chloride on blood pressure, body fluids, electrolytes, renal function, and serum lipids ofnormotensive man. J Lab Clin Med 1976; 87: 418-34.Kirkendall WM, Connor WE, Abboud F, et al. The effect of dietary sodium chloride on blood pressure, body fluids, electrolytes, renal function, and serum lipids ofnormotensive man. J Lab Clin Med 1976; 87: 418-34.Kjeldsen SE, DahlofB, Devereux RB, et al. Effects oflosartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy. JAMA 2002; 28S: 1491-8.Kjeldsen SE, DahlofB, Devereux RB, et al. Effects oflosartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy. JAMA 2002; 28S: 1491-8.Cushman WC, Brady WE, Gazdick LP, Zeldin RK. The effect of losartan-based treatment on isolated systolic hypertension. J Clin Hypertension 2002; 4: 101-7.Cushman WC, Brady WE, Gazdick LP, Zeldin RK. The effect of losartan-based treatment on isolated systolic hypertension. J Clin Hypertension 2002; 4: 101-7.Franklin SS, Larson MG, Khan SA, et al. Does the relation of blood pressure to coronary disease risk. change with aging? The Framinham Heart Study. Circulation 2001; 103: 1245-9.Franklin SS, Larson MG, Khan SA, et al. Does the relation of blood pressure to coronary disease risk. change with aging? The Framinham Heart Study. Circulation 2001; 103: 1245-9.Neutel, 1M, Elliott WJ, Izzo JL Jr, et al. Antihypertensive efficacy of olmesartan medoximil, a new angiotensin II receptor antagonist, as assessed by ambulatory blood pressure measurements. J Clio Hypertens 2002; 2: 325-31.Neutel, 1M, Elliott WJ, Izzo JL Jr, et al. Antihypertensive efficacy of olmesartan medoximil, a new angiotensin II receptor antagonist, as assessed by ambulatory blood pressure measurements. J Clio Hypertens 2002; 2: 325-31.Puchler K, Laeis P, Stumpe KO. Blood pressure response, but not adverse event incidence, correlates with dose of angiotensin II antagonist. J Hypertension 2001; 19(Suppll): S41-8.Puchler K, Laeis P, Stumpe KO. Blood pressure response, but not adverse event incidence, correlates with dose of angiotensin II antagonist. J Hypertension 2001; 19(Suppll): S41-8.Sealey J, Blumenfeld J, Bell M, et al. Presidential address. On the renal basis for essential hypertension: nephron heterogeneity with discordant renin secretion and sodium excretion causing a hypertensive vasoconstriction-volume relationship. J Hypertens 1988; 6: 763-77.Sealey J, Blumenfeld J, Bell M, et al. Presidential address. On the renal basis for essential hypertension: nephron heterogeneity with discordant renin secretion and sodium excretion causing a hypertensive vasoconstriction-volume relationship. J Hypertens 1988; 6: 763-77.Bakris GL, Siomos M, Richardson D, et al. ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. Val-K Study Group. Kidney Int 2000; 58: 2084-92.Bakris GL, Siomos M, Richardson D, et al. ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. Val-K Study Group. Kidney Int 2000; 58: 2084-92.Schmidt A, Gruber U, Bohmig G, et al. The effect of ACE inhibitor and angiotensin II receptor antagonist therapy on serum uric acid levels and potassium homeostasis in hypertensive renal transplant recipients treated with CsA. Nephrcl Dial Transplant 2001; 16: 1034-7.Schmidt A, Gruber U, Bohmig G, et al. The effect of ACE inhibitor and angiotensin II receptor antagonist therapy on serum uric acid levels and potassium homeostasis in hypertensive renal transplant recipients treated with CsA. Nephrcl Dial Transplant 2001; 16: 1034-7.Tanabe A, Naruse M, Arai K, et a1. Gene expression and roles of angiotensin II type 1 and 2 receptors in adrenals. Horm Metab Res 1998; 30: 490-5.Tanabe A, Naruse M, Arai K, et a1. Gene expression and roles of angiotensin II type 1 and 2 receptors in adrenals. Horm Metab Res 1998; 30: 490-5.Naruse M, Tanabe A, Sato A, et al. Aldosterone breakthrough during angiotensin receptor antagonist therapy in stroke-prone spontaneously hypertensive rats. Hypertension 2002; 40: 28-33.Naruse M, Tanabe A, Sato A, et al. Aldosterone breakthrough during angiotensin receptor antagonist therapy in stroke-prone spontaneously hypertensive rats. Hypertension 2002; 40: 28-33.

The authors declare that there are no conflicts of interest present.