[Arguments in favor of postsynaptic antagonism by captopril (SQ 14,225) in the perfused kidney].
The potential antagonistic effect of high doses of Captopril on renal vascular response to exogenous administration or nerve stimulated release of norepinephrine (NE) was assessed in isolated blood-free perfused rat and rabbit kidneys respectively. At the doses of 0,09 mM and 0,45 mM in rat kidney, captopril blunted significantly the vasoconstrictor effect of exogenous NE (20, 40 and 100 ng) whilst responses to angiotensin II (2,5 and 10 ng) were slightly reduced at the highest dose and responses to serotonin (20, 40 and 100 mg) remained unaffected by either doses of Captopril. The other effective converting enzyme inhibitor, SQ 20881 had no effect on pressor responses to norepinephrine at similar doses. In preliminary rabbit studies, a likewise blunting of pressor effect of exogenous norepinephrine was obtained at the doses of captopril of 0,23 mM and 0,45 mM. Furthermore, these doses of captopril had no effect on either basal or nerve-stimulated NE release whilst nerve-stimulated vasoconstriction was significantly and reversibly blunted at both doses. These studies suggest a) that the inhibitory effect of Captopril on NE renal vasoconstriction in not primarily dependent on converting enzyme inhibition; b) that the observed alpha-antagonistic activity of high doses of captopril occurs principally at a post-junctional level.
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D007668:Kidney / Q000294:innervation*; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D010477:Perfusion; D011392:Proline / Q000031:analogs & derivatives*; D011817:Rabbits; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects*; D013045:Species Specificity; D013569:Synapses / Q000187:drug effects*; D013722:Teprotide / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D000804:Angiotensin II; D011392:Proline; D002216:Captopril; D013722:Teprotide; D009638:Norepinephrine
Arguments en faveur d'un antagonisme post-synaptique du captopril (SQ 14225) dans le rein perfusé.