The response of plasma levels of active and inactive renin to haemorrhage was investigated in sheep with indwelling artery and vein catheters. In conscious animals, loss of 10% of estimated blood volume over a 5 min period increased plasma active renin by a mean of 59%, a surprisingly small change. Plasma inactive renin also increased, but only by 86%. Maximum increases in both forms of renin occurred within 1 h of the haemorrhage. The effects of an equivalent blood loss were investigated in pentobarbitone-anaesthetized sheep maintained in an upright posture using padded slings. Anaesthesia per se had no effect on plasma active or inactive renin. In anaesthetized sheep, 3 h after haemorrhage, plasma active renin had increased by 403% and inactive renin by 299% above control values, but a plateau (maximum) response was not reached during this time. In both conscious and anaesthetized animals the haemorrhage-induced increases in active and inactive renin occurred in parallel. It appears that haemorrhage of this intensity is a comparatively mild stimulus to increase plasma renin concentration in conscious sheep but is much more effective in anaesthetized animals. This may be linked to anaesthetic-induced increases in prostaglandin synthesis within the kidney.

I . 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.2. 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.3. Plasma active and inactive renin changed in parallel. Both were significantly increased within I 5 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.4. 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.5. Verapamil did not alter urine flow or sodium and potassium excretion rates. 6. 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.