Renal hemodynamics and renal kinins after angiotensin-converting enzyme inhibition.
The effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on the renal kallikrein-kinin system and renal hemodynamics was studied in anesthetised dogs for 45 min after captopril administration. ACE inhibition was confirmed by increases in blood angiotensin I (AI) and plasma renin activity and a 20-fold decrease in sensitivity of the blood pressure and renal blood flow dose-response curves to AI. Captopril (1.5 mg . kg-1, i.v.) led to an increase in renal blood flow of 56 +/- 13 ml/min-1 (P less than .01) despite a fall in mean arterial pressure of 17 +/- 5 mm Hg (P less than 0.005). Glomerular filtration rate did not change whereas the filtration fraction decreased (p less than 0.005). The hypotension and renal vasodilation were accompanied by an increase in urinary kinin excretion (P less than .025) but no acute change in circulating kinins or urinary kallikrein excretion. Urine volume and urinary sodium and potassium excretion increased. To determine the contribution of the renin-angiotensin system to these hemodynamic changes, were gave captopril to a further group of dogs during a continuous infusion of the competitive angiotensin II (AII) receptor antagonist sar1ile8-AII (2.5 micrograms/kg/min). Subsequent ACE inhibition was still associated with an increase in renal blood flow of 35 +/- 17 ml/min-1 (P less than 0.05), decrease with a mean arterial pressure by 11 +/- 4 mm Hg (P less than 0.025). These results suggest that ACE inhibition increases levels of intra-renal kinins and that decreased degradation of these tissue vasodilator peptides may contribute significantly to the acute renal vasodilation and hypotensive effect of captopril.
D000804:Angiotensin II / Q000097:blood / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure; D002216:Captopril / Q000494:pharmacology*; D004285:Dogs; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007705:Kinins / Q000378:metabolism* / Q000652:urine; D011392:Proline / Q000031:analogs & derivatives*; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D014655:Vascular Resistance
D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D000804:Angiotensin II; D011392:Proline; D002216:Captopril; D012083:Renin