Conlin P R, Seely E W, Hollenberg N K, Williams G H
Endocrinology-Hypertension Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
Endocr Res. 1998 May;24(2):127-39. doi: 10.1080/07435809809135523.
Calcium channel blockers as a class reduce both vascular resistance and systemic blood pressure. However, it is not known if different classes of calcium channel blockers have similar effects on the renin-angiotensin-aldosterone system. We investigated vascular and adrenal responses to endogenous and exogenous angiotensin II in normotensive subjects before and after receiving isradipine or diltiazem. Subjects achieved low salt balance before study and underwent an angiotensin II infusion and upright posture study. After re-achieving salt balance the subjects received either isradipine (n=10), or diltiazem (n=7) for three days before repeating the study. Both agents lowered blood pressure and significantly shifted the dose response relationship of angiotensin II and mean blood pressure (P<0.01). In contrast, aldosterone secretion in response to upright posture and angiotensin II infusion was significantly reduced (P<0.01) by isradipine but not by diltiazem. The in vitro effects of both agents on aldosterone secretion from bovine adrenal glomerulosa cells paralleled the in vivo observations showing that angiotensin II-stimulated aldosterone secretion was markedly blunted by isradipine and minimally by diltiazem. These results suggest a tissue specificity for the effects of different classes of calcium channel blockers. Dihydropyridine calcium channel blockers may exert their antihypertensive effect by blocking both vascular and adrenal responses to angiotensin II.
钙通道阻滞剂作为一类药物,可同时降低血管阻力和全身血压。然而,不同类别的钙通道阻滞剂对肾素-血管紧张素-醛固酮系统是否具有相似作用尚不清楚。我们研究了服用伊拉地平或地尔硫䓬前后,正常血压受试者对内源性和外源性血管紧张素II的血管及肾上腺反应。受试者在研究前实现低盐平衡,并接受血管紧张素II输注及直立姿势研究。在再次实现盐平衡后,受试者在重复研究前接受伊拉地平(n = 10)或地尔硫䓬(n = 7)治疗三天。两种药物均降低了血压,并显著改变了血管紧张素II与平均血压之间的剂量反应关系(P < 0.01)。相比之下,伊拉地平显著降低了因直立姿势和血管紧张素II输注引起的醛固酮分泌(P < 0.01),而地尔硫䓬则未降低。两种药物对牛肾上腺球状带细胞醛固酮分泌的体外作用与体内观察结果一致,表明伊拉地平显著抑制血管紧张素II刺激的醛固酮分泌,而地尔硫䓬的抑制作用最小。这些结果提示不同类别的钙通道阻滞剂作用具有组织特异性。二氢吡啶类钙通道阻滞剂可能通过阻断血管和肾上腺对血管紧张素II的反应来发挥其降压作用。