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Evidence That the Renal Pressor Substance of Grollman Is Related to Angiotensin I

Grollman and coworkers have found a “renal pressor substance” in the renal vein plasma of patients with renovascular hypertension. When injected into nephrectomized, ganglion-blocked rats, it evokes a pressor response similar to that of angiotensin. Detection of this substance has proved useful in predicting the normalization of blood pressure seen after surgical correction of renal artery stenosis. In order to characterize this factor, simultaneous bioassays and radioimmunoassays for angiotensin I were performed on renal vein plasma and plasma extracts from patients with renovascular hypertension. Whenever pressor activity was found on bioassay, a comparable amount of preformed immunoreactive angiotensin I (1 to 10 ng/ml) was found in renal venous plasma from the kidney with a stenotic artery. In vitro incubation of the “renal pressor substance” with an antiserum to angiotensin I completely inactivated it. The “renal pressor substance” was transformed by “converting enzyme” to a substance which retained the pressor activity but lacked the immunoreactivity of angiotensin I—presumably angiotensin II. The pressor radioimmunoassayable material in plasma was relatively nondialyzable and was not well adsorbed on Dowex 50W-X2 ion exchange resin; angiotensin I behaved similarly when added to plasma. It is suggested that these phenomena are related to the binding of angiotensin I to a plasma protein. After adding 125I-angiotensin I to plasma, the radioactivity was found to migrate with α2 globulin on electrophoresis and to precipitate with an α2 globulin antigen-antibody complex on immunoelectrophoresis. It is concluded that the “renal pressor substance” of Grollman is preformed angiotensin I bound to α2 globulin.