Partial blockade of neurotensin-induced hypotension in rats by nephrectomy captopril and saralasin. Possible mechanisms

Abstract We have assessed the influence of acute bilateral nephrectomy, of captopril and saralasin, on the hypotensive activity of neurotensin (NT) and of various hypotensive drugs in pentobarbital-anesthetized rats. The results show that the hypotensive activity of NT and of compound 48 80 ( C48 80 ), in contrast to that of histamine, of 5-hydroxytryptamine and of hexamethonium, is markedly reduced, especially for NT, in nephrectomized as compared to sham operated rats. The pretreatment of rats with captopril (10 mg kg −1 , i.v.) or with saralasin (20 μg kg −1 min −1 , i.v.) was found to inhibit significantly the hypotensive activity of NT and of C48 80 . Adrenalectomy restored partially the hypotensive activity of NT in nephrectomized rats. The potent vasopressin antagonst [d(CH 2 ) 5 Tyr(Me)AVP] did not alter the refractoriness of nephrectomized rats to the hypotensive activity of NT. Neither nephrectomy nor saralasin were found to interfere with the ability of NT or of C48 80 to evoke an increase of plasma histamine level or of the hematocrit. The results were interpretated as an indication that NT produces part of its hypotensive effect in anesthetized rats by reducing the activity of the reninangiotensin system. The results also suggest that part of the refractoriness of nephrectomized rats to the hypotensive activity of NT could be due to the release of catecholamines from adrenal glands by NT. Endogenous vasopressin does not appear to contribute to the refractoriness of nephrectomized rats to the hypotensive action of NT.