Antihypertensive Effect of Calcium Entry Blockers

本研究旨在阐明钙离子通道阻滞剂在麻醉犬和去髓大鼠的降压作用。肾内注入钙离子通道阻滞剂硝苯地平和CD-349可显著增加尿流率和尿钠、钾排泄率，但对心率、肾小球滤过率和滤过分数无明显影响。药物可降低尿液渗透压。注入肾脏的血流量增加。这些结果表明，硝苯地平和CD-349对肾小管对钠和水的重吸收有显著影响(参考文献1)。肾内注射硝苯地平和CD-349可剂量依赖性地抑制肾内注射血管紧张素II或去甲肾上腺素引起的肾血管收缩，但不能抑制刺激肾神经引起的收缩。此外，…观察到肾内注射硝苯地平而不是乙酰胆碱可引起更大的肾血管扩张。对侧肾脏灌流压降低时更明显，导致血浆肾素活性和血浆AII浓度升高(参考文献2)。在腹痛大鼠，硝苯地平抑制对α2肾上腺素能受体激动剂B-HT920和AII的血管收缩反应，但不能抑制α1肾上腺素能受体激动剂甲氧胺和加压素的收缩反应。CD-349可降低上述激动剂的升压反应。经钙通道促进剂Bay K 8644处理后，CD-349对AII、B-HT920和加压素的抑制作用被拮抗。这些结果表明，钙拮抗剂阻断钙内流对所有肾上腺素能受体介导的血管收缩反应敏感，但α1肾上腺素能受体激动剂引起的血管收缩主要不依赖于钙内流。跨细胞钙内流可能是α-2激动剂B-HT920和AII引起血管收缩的共同途径。较少

The present study was performed to clarify the antihypertensive effects of calcium entry blockers using anesthetized dogs and pithed rats.1. Intrarenal infusion of nifedipine and CD-349, calcium entry blockers, produced marked increase in urine flow rate and in urinary sodium and potassium excretion rates of the infused kidney without changes in heart rate, glomerular filtration rate and filtration fraction. Urinary osmolarity was decreased by the drugs. The blood flow to the infused kidney was increased. These results suggest that nifedipine and CD-349 have striking effects on the reabsorption of sodium and water by the renal tubule (Reference 1).2. Intrarenal infusion of nifedipine and CD-349 dose-dependently suppressed the renal vasoconstriction induced by intrarenal injections of angiotensin II (AII) or norepinephrine but not that by renal nerve stimulation. Furthermore, a greater renal vasodilation induced by intrarenal bolus injections of nifedipine but not acetylcholine was obse … More rved during the reduction of the perfusion pressure of the contralateral kidney, which resulted in an increase in plasma renin activity and plasma AII concentration (Reference 2).3. In pithed rats, nifedipine inhibited the vasoconstrictor responses to alpha-2-adrenoceptor agonist B-HT 920, and AII but not to the alpha-1-adrenoceptor agonist methoxamine, and vasopressin. CD-349 reduced the pressor responses to all the above agonists. After pretreatment of calcium channel promotor Bay K 8644, the inhibition of CD-349 observed for AII, B-HT 920 and vasopressin was antagonized. These results suggest that AII-, alpha-2-adrenoceptor-mediated vasoconstrictions are sensitive to calcium entry blockade with calcium antagonists, but the vasoconstriction induced by the alpha-1-adrenoceptor-mediated agonist is not primarily dependent upon an influx of calcium. And it is possible that transcellular calcium influx may be common pathway in the vasoconstriction elicited by alpha-2-agonist B-HT 920 and AII. Less