Specificity of renal vasodilation with captopril: saralasin prevents the response in the DOCA-treated, salt-loaded rabbit.
A prominent action of converting enzyme inhibitors, such as captopril, is a reduction in angiotensin II formation, but interpretation of responses has been complicated by the potential for such agents to reduce bradykinin degradation and promote prostaglandin release. To assess the specificity of the action of captopril, we pretreated rabbits with desoxycorticosterone and a high sodium intake, to suppress the renin-angiotensin system and thus maximize the renal vascular responses which might be unrelated to angiotensin II. Captopril was infused intravenously in graded dosage from 10 to 3,000 microgram/kg, and renal blood flow measured with an electromagnetic flowmeter. Despite suppression of the renin system, captopril increased renal blood flow from 3.7 +/- 0.5 to 5.3 +/- 0.8 ml/g/min (p less than .001) in 7 rabbits. In 6 additional rabbits, captopril was superimposed on a saralasin infusion (1.0 microgram/kg/min) in a dose sufficient to block response to endogenous angiotensin II. Saralasin prevented entirely the renal vasodilator response to captopril. Two surprising conclusions derive from this study: first, the renal vasodilator response to captopril appears to be specific for a reduction in angiotensin II formation; second, endogenous angiotensin appears to contribute to renal vascular tone, at least when anesthesia is employed, even when the renin system has been suppressed by a combination of a high sodium intake and desoxycorticosterone.
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000502:physiology; D000818:Animals; D002216:Captopril / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D011817:Rabbits; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012504:Saralasin / Q000494:pharmacology*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000804:Angiotensin II; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D011392:Proline; D002216:Captopril; D012504:Saralasin