Roles of renal and vascular renin in spontaneous hypertension and switching of the mechanism upon nephrectomy. Lack of hypotensive effects of inhibition of renin, converting enzyme, and angiotensin II receptor blocker after bilateral nephrectomy. Inhibitors of angiotensin converting enzyme, renin, and the angiotensin II (Ang II) receptor lower the blood pressure of spontaneously hypertensive rats (SHR) used as a model of essential hypertension. Since their plasma renin levels were normal or subnormal, renin in the vascular tissue was considered to play a key role in the maintenance of the hypertension. To clarify the source and localization of renin in SHR, antirenin antibodies, the converting enzyme inhibitors delapril, enalapril, and the Ang II receptor antagonist DuP 753 were administered to intact and bilaterally nephrectomized SHR and their normotensive controls. The efficient hypotensive action of the renin antibody indicated that renin of renal origin is a dominant factor. Gradual but complete disappearance of antihypertensive action of these inhibitors of the renin-angiotensin system upon bilateral nephrectomy indicated the importance of membrane-associated renin of the renal origin and angiotensin converting enzyme in the maintenance of the spontaneous hypertension. 