RENAL TISSUE ANGIOTENSINS DURING CONVERTING-ENZYME INHIBITION IN THE SPONTANEOUSLY HYPERTENSIVE RAT

To compare the effects of an angiotensin-converting enzyme inhibitor o n circulating and tissue renin-angiotensin system (RAS), we measured d ifferent RAS parameters during the first day of treatment (Day1) as we ll as after two weeks of treatment (Day14). Ramipril was given orally once daily to adult male spontaneously hypertensive rats (SHR). Renin activity (RA), angiotensin converting enzyme (ACE) activity and levels of angiotensin I (ang I) and angiotensin II (ang II) in the plasma, r enal cortex and renal medulla were assessed at Day1 and Day14 of the t reatment. In the plasma, both RA and ang I increased 10 to 15 fold one to four hours after acute as well as at Day14 of ramipril treatment a nd then returned to basal values within 24 hours. Plasma ang II levels were not significantly decreased at Day1 or Day14. The decrease in th e ang II/ang I ratio suggested a sustained inhibition of plasma ACE at Day14. In the renal cortex and medulla, a clearly different pattern w as observed: in ramipril treated rats, RA in the renal cortex and medu lla did not change at Day1 but at Day14 we observed a slight and susta ined increase in RA. Despite very high basal levels of RA, ang I level s in the renal cortex were comparable to those in the plasma. The ang I level increased only one-fold one hour after ramipril intake at Day1 and Day14. This suggests that angiotensinogen may have a limiting rol e in the synthesis of ang I in the kidney. Ang II levels were slightly higher in the renal cortex and medulla than in the plasma suggesting local synthesis of the peptide. In the kidney, ang II levels decreased one and four hours after the acute or prolonged ramipril treatment an d the ang II/ang I ratio was reduced at the same time. Our results sho w that the responses of the plasma and kidney components of the RAS to ACE inhibition are different in the plasma and the kidney suggesting that the circulating and tissue RAS are at least in part independent.