Alterations in renal vascular reactivity induced by chronic central administration of captopril in the spontaneously hypertensive rat.
We have previously demonstrated that chronic intracerebroventricular (ICV) administration of captopril attenuates the development of hypertension in young SHR in association with a depression in whole animal reactivity to vasoactive agents and an increased baroreflex sensitivity. In the present study we analyzed vascular reactivity in perfused kidneys from SHR treated with captopril or vehicle to determine whether the depression in reactivity was due to changes in baroreflex activity or an effect on the vasculature. Captopril (1.25 micrograms/hr) was infused (osmotic mini pumps) for 4 weeks. Vascular reactivity to norepinephrine, angiotensin and vasopressin was assessed in isolated kidneys perfused with an artificial medium at constant flow. SHR treated with ICV captopril showed a significantly lower arterial pressure and basal renal vascular resistance than SHR treated with ICV vehicle or IV captopril. In addition, these rats showed decreased vascular reactivity to all vasoactive agents tested as signified by a shift in the dose-response curves to the right with an increase in threshold (ED16) and ED50. Kidneys from WKY treated with ICV captopril also showed a decrease in vascular reactivity in comparison to WKY treated with ICV vehicle. Our data suggest that captopril, through a central action, attenuates the development of hypertension by decreasing vascular reactivity to vasoconstrictors.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage*; D004353:Drug Evaluation, Preclinical; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012018:Reflex / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D002216:Captopril