[Effects of conversion enzyme inhibitors on the synthesis of angiotensin II by the isolated rat kidney].
On the isolated perfused rat kidney, angiotensin-converting-enzyme activity was evaluated by two approaches: one, biochemical, through the measurements of the enzymatic activity on renal homogenate, the other, pharmacological, through the vasoconstrictor response to angiotensin I. Renal tissue angiotensin-converting-enzyme activity was not modified by setting the kidney under perfusion with a modified Krebs-Henseleit solution but was inhibited after addition of captopril into the perfusion medium (10(-5) M, 100 p. 100 inhibition) or after pretreatment of the animals with ramipril (10 mg/kg/day over 3 weeks, per os, 60 p. 100 inhibition). On the isolated perfused rat kidney, angiotensin I and angiotensin II induced a concentration dependent renal vasoconstriction (EC50 = 1.05 +/- 0.18 X 10(-8) and 0.11 +/- 0.05 X 10(-8) M) which was competitively antagonized by saralasin, an angiotensin II receptor antagonist. Addition of angiotensin-converting-enzyme inhibitors to the perfusion medium (captopril or ramiprilat, 10(-5) M) or pretreatment of the animals with ramipril (50 mg/kg, i.p. the day before or 10 mg/kg/day over 3 weeks, per os) only shifted the angiotensin I concentration-response curve to the right by a factor 3 to 4. The residual vasoconstrictor effect of angiotensin I was abolished by 10(-5) M saralasin and remains linked to a local generation of angiotensin II. Our results suggest that, on the isolated perfused rat kidney, besides the angiotensin-converting-enzyme, an iso-enzyme may also be able to generate angiotensin II.
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D008297:Male; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D017257:Ramipril
Effets des inhibiteurs de l'enzyme de conversion sur la synthèse d'angiotensine II par le rein de rat isolé.