The antihypertensive function of the kidney. Its elucidation by captopril plus unclipping

Unclipping the one-kidney, one-clip hypertensive rat during a free flow of urine caused the blood pressure to return to normal levels within about 3 hours. We found that administration of captopril plus unclipping caused the blood pressure to return to normal in minutes (17 +/- 4). Ureterocaval anastomosis plus captopril plus unclipping also caused the blood pressure to return to normal in minutes (8.8 +/- 2). Thus, the potentiation of the drop in blood pressure does not seem to be due to a volume effect. Administration of indomethacin and aprotinin did not prevent a rapid decline of the blood pressure after unclipping, but the decline was less rapid than that occurring after captopril and unclipping, which suggests that prostaglandin may have some effect on this mechanism. Saralasin administration did not potentiate the antihypertensive action of captopril plus unclipping. Chemical papillectomy prevented the drop in blood pressure after unclipping. The bolus dose of captopril to the hypertensive rat often caused a transient depressor effect resembling that due to the antihypertensive neutral renomedullary lipid, which suggests secretion of this lipid into the blood. The renomedullary interstitial cells accumulated large lipid granules after captopril administration. These cells also degranulated after unclipping. These findings are consistent with the hypothesis that the renal papilla secretes an antihypertensive hormone after unclipping. At present, antihypertensive neutral renomedullary lipid is the main putative hormone.