血管紧张素II受体拮抗剂奥美沙坦对正常受试者的急性血管效应：与肾素-醛固酮系统的关系

Acute vascular effects of the angiotensin II receptor antagonist olmesartan in normal subjects: relation to the renin-aldosterone system.

作者信息

Resnick Lawrence M, Catanzaro Daniel, Sealey Jean E, Laragh John H

机构信息

Hypertension and Cardiovascular Centers, Division of Cardiovascular Pathophysiology, Cornell University Weill College of Medicine, 525 E 68th Street/Starr 4 Pavilion, New York, NY 10021, USA.

出版信息

Am J Hypertens. 2004 Mar;17(3):203-8. doi: 10.1016/j.amjhyper.2003.12.003.

DOI:10.1016/j.amjhyper.2003.12.003

PMID:15001191

Abstract

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 medoximil to 12 unmedicated normotensive subjects. In the basal state, SVR was inversely related to UNaV (r = -0.3, P =.04); the greater the UNaV, the more vasodilated the subject. Indices of arterial compliance, both C1 (r = -0.32, P =.03) and C2 (r = -0.35, P =.02) were inversely related to the basal PRA. Renin also predicted olmesartan-induced changes in C1 (r = 0.43, P =.004) and C2 (r = 0.33, P =.04). The greater the basal PRA, the less the arterial compliance, and the more compliance improved after olmesartan. Both systolic (P =.003) and diastolic (P <.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 =.012; diastolic BP: r = -0.561 P <.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 =.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.

摘要

血管紧张素受体阻滞剂（ARB）的临床效果与周围肾素系统活性之间的关联程度仍未明确界定。因此，我们对12名未接受药物治疗的血压正常受试者在服用单剂量安慰剂以及5毫克、20毫克和40毫克ARB奥美沙坦酯之前和之后1小时、2小时、4小时及24小时测量了血压（BP）、大（C1）和小（C2）动脉顺应性、全身血管阻力（SVR）、血浆肾素活性（PRA）以及钠（UNaV）和醛固酮的24小时尿排泄量。在基础状态下，SVR与UNaV呈负相关（r = -0.3，P = 0.04）；UNaV越高，受试者血管舒张越明显。动脉顺应性指标，无论是C1（r = -0.32，P = 0.03）还是C2（r = -0.35，P = 0.02）均与基础PRA呈负相关。肾素还可预测奥美沙坦引起的C1（r = 0.43，P = 0.004）和C2（r = 0.33，P = 0.04）变化。基础PRA越高，动脉顺应性越低，而服用奥美沙坦后顺应性改善越明显。与安慰剂相比，奥美沙坦使收缩压（P = 0.003）和舒张压（P < 0.0001）均显著下降（时间因素的多变量方差分析），且观察到基础PRA与奥美沙坦引起的血压变化之间存在关联（收缩压：r = -0.414，P = 0.012；舒张压：r = -0.561，P < 0.0001）——初始PRA越高，奥美沙坦降低血压的幅度越大。此外，血压下降越多，PRA相应升高越多（r = -0.44，P = 0.007）。最后，与安慰剂相比，每剂奥美沙坦均使醛固酮排泄量下降（sig = 0.05）。我们得出结论：1）UNaV与SVR的负相关说明了容量因素与收缩因素在维持正常血压中的相互作用；2）PRA是正常个体动脉顺应性以及对ARB奥美沙坦反应的生理决定因素。测量PRA可能有助于预测个体受试者的临床ARB反应。