[Renal tissue angiotensins during converting enzyme inhibition of angiotensin I in spontaneously hypertensive rat].
To compare the effects of an angiotensin-converting enzyme inhibitor on circulating and tissue renin-angiotensin system, we measured different renin-angiotensin system parameters during the first day of treatment (Day 1) as well as after two weeks of treatment (Day 14). Ramipril was given orally once daily to adult male spontaneously hypertensive rats. Renin activity, angiotensin-converting enzyme activity and levels of angiotensin I and angiotensin II in the plasma, renal cortex and renal medullar were assessed at Day 1 and Day 14 of the treatment. In the plasma, both renin activity and angiotensin I increased 10 to 15 fold one to four hours after acute as well as at Day 14 of ramipril treatment and then returned to basal values within 24 hours. Plasma angiotensin II levels were not significantly decreased at Day 1 or Day 14. The decrease in the angiotensin II/angiotensin I ratio suggested a sustained inhibition of plasma angiotensin-converting enzyme at Day 14. In the renal cortex and medulla, a clearly different pattern was observed: in ramipril treated rats, renin activity in the renal cortex and medulla did not change at Day 1 but at Day 14 we observed a slight and sustained increase in renin activity. Despite very high basal levels of renin activity, angiotensin I levels in the renal cortex were comparable to those in the plasma. The angiotensin I level increased only one-fold one hour after ramipril intake at Day 1 and Day 14. This suggests that angiotensinogen may have a limiting role in the synthesis of angiotensin I in the kidney. Angiotensin II levels were slightly higher in the renal cortex and medulla than in the plasma suggesting local synthesis of the peptide. In the kidney, angiotensin II levels decreased one and four hours after the acute or prolonged ramipril treatment and the angiotensin II/angiotensin I ratio was reduced at the same time. Our results show that the responses of the plasma and kidney components of the renin-angiotensin system to angiotensin-converting enzyme inhibition are different in the plasma and the kidney suggesting that the circulating and tissue renin-angiotensin system are at least in part independent.
Ingert
C
C
Institut de pharmacologie et de médecine expérimentale, faculté de médecine, université Louis-Pasteur, Strasbourg.
Grima
M
M
Michel
B
B
Barthelmebs
M
M
Imbs
J L
JL
D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006977:Hypertension, Renal / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D012083:Renin; D017257:Ramipril