Verapamil-induced secretion of active and inactive renin in conscious sheep

Regulation of plasma active and inactive renin was investigated using conscious sheep with indwelling artery, vein and bladder catheters. Control and experimental studies were carried out in the same animals on different days. The calcium antagonist drug verapamil was given as an initial bolus injection (0.5 mg/kg) followed by a continuous infusion (0.1 mg/kg per h) over a 2.5 h period. Plasma active and inactive renin changed in parallel. Both were significantly increased within 15 min of the initial drug dose and both attained a peak increase after 45 min. Thereafter, the two forms of renin returned to basal levels despite continued infusion of the drug. Effective renal plasma flow (CPAH) was also transiently increased by verapamil and followed a similar time course to changes in plasma active and inactive renin concentration. Arterial blood pressure, however, remained suppressed by verapamil for the duration of the study. Verapamil did not alter urine flow or sodium and potassium excretion rates. These results are discussed in relation to the possible link between intrarenal haemodynamics and renin secretion in conscious and in anaesthetized animals and also in relation to the concept that variation in the relative amounts of active and inactive renin secreted in differing physiological situations represents a mechanism for regulating the renin-angiotensin system.