Pedersen O L, Mikkelsen E, Christensen N J, Kornerup H J, Pedersen E B
Eur J Clin Pharmacol. 1979 May 21;15(4):235-40. doi: 10.1007/BF00618511.
Acute sublingual administration of nifedipine 10--20 mg to 13 hypertensive patients caused a rapid decrease in blood pressure (BP) and a concomitant increase in heart rate (HR), plasma noradrenaline (NA) and plasma renin activity (PRA); there was no significant change in plasma adrenaline (A) or aldosterone (ALDO). Basal PRA was the major determinant of the rise in PRA, as a close correlation was present between the basal value and the increase caused by nifedipine (r = 0.92), p less than 0.001). The rise in PRA was also correlated with the plasma concentration of nifedipine after 60 min (r = 0.80, p less than 0.01), but it was not correlated with the decrease in BP, the rise in HR or the increase in NA. Nifedipine 30--60 mg daily for 6 weeks caused a reduction in mean BP from 133 to 113 mmHg (p less than 0.001). Body weight and serum potassium decreased but no consistent change was noted in NA, PRA, ALDO or 24 h-excretion of catecholamines. A significant correlation was present between the change in NA and that in PRA (r = 0.74, p less than 0.01). The alterations in the various parameters in the acute and chronic studies were not correlated. The findings indicate that different regulatory mechanisms are activated during acute and chronic administration of nifedipine. It is suggested that an initial rise in sympathetic activity gradually decreases during prolonged therapy, but it still remains a determinant of PRA.
对13名高血压患者急性舌下含服10 - 20毫克硝苯地平，可使血压（BP）迅速下降，并伴随心率（HR）、血浆去甲肾上腺素（NA）和血浆肾素活性（PRA）升高；血浆肾上腺素（A）或醛固酮（ALDO）无显著变化。基础PRA是PRA升高的主要决定因素，因为基础值与硝苯地平引起的升高之间存在密切相关性（r = 0.92，p < 0.001）。PRA的升高也与60分钟后硝苯地平的血浆浓度相关（r = 0.80，p < 0.01），但与血压下降、心率升高或NA升高无关。每日服用30 - 60毫克硝苯地平，持续6周，可使平均血压从133毫米汞柱降至113毫米汞柱（p < 0.001）。体重和血清钾下降，但NA、PRA、ALDO或儿茶酚胺的24小时排泄量无一致变化。NA变化与PRA变化之间存在显著相关性（r = 0.74，p < 0.01）。急性和慢性研究中各项参数的变化不相关。研究结果表明，硝苯地平急性和慢性给药期间激活了不同的调节机制。提示在长期治疗过程中，交感神经活性最初升高后逐渐下降，但仍是PRA的一个决定因素。
