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Application of a Radioimmunoassay for Angiotensin I to the Physiologic Measurements of Plasma Renin Activity in Normal Human Subjects¹

Department of Medicine, Harvard Medical School, and the Cardiac Unit, Medical Service, Massachusetts General Hospital Newton, Massachusetts
Department of Medicine, Tufts University School of Medicine, and the Medical Service, Newton-Wellesley Hospital Newton, Massachusetts

A radioimmunoassay for angiotensin I and its application to the determination of renin activity is described. The assay employs antibodies raised to copolymers of angiotensin I and succinylated poly-L-lysine. Angiotensin labeled with ¹²⁵I and purified by high voltage paper electrophoresis is employed as a tracer. Incubation is carried out in plasma in the presence of 3 metal binding reagents which serve to inhibit effectively proteolytic attack on angiotensin I. Immunoassay of generated angiotensin I is carried out directly on plasma diluted 1:20. Fifteen normal volunteers were studied on a metabolic ward at 2 levels of Na intake, during recumbency and upright posture, and following the administration of furosemide. Renin activity increased with Na restriction, was significantly higher on upright activity during both normal and restricted Na intake, and was most markedly elevated following the diuretic. Renin values obtained by immunoassay of angiotensin I correspond closely to those observed by bioassay in similar metabolic studies. The immunoassay provides the advantages of relative simplicity, specificity and reproducibility.

Supported by USPHS Grants AI-04967, AM-11019, AM-4501, HE-11015, HEP-06664, and the Heart and Lung Foundation.

¹ A preliminary account of this investigation was presented at the annual meeting of the American Heart Association, November 1968, and as part of a Seminar in Medicine at the Beth Israel Hospital, Boston, Mass. A transcription of the latter has been published (1).

Received May 7, 1969.

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				J. A. Mitas II, R. Holle, S. B. Levy, and R. A. Stone Racial Analysis of the Volume-Renin Relationship in Human Hypertension Arch Intern Med, February 1, 1979; 139(2): 157 - 160. [Abstract] [PDF]

				W. M. Kirkendall, J. J. Hammond, J. C. Thomas, M. L. Overturf, and A. Zama Prazosin and Clonidine for Moderately Severe Hypertension JAMA, December 1, 1978; 240(23): 2553 - 2556. [Abstract] [PDF]

				Z. Farfel, A. Iaina, T. Rosenthal, U. Waks, S. Shibolet, and J. Gafni Familial Hyperpotassemia and Hypertension Accompanied by Normal Plasma Aldosterone Levels: Possible Hereditary Cell Membrane Defect Arch Intern Med, December 1, 1978; 138(12): 1828 - 1832. [Abstract] [PDF]

				Z. Farfel, A. Iaina, J. Levi, and J. Gafni Proximal Renal Tubular Acidosis: Association With Familial Normaldosteronemic Hyperpotassemia and Hypertension Arch Intern Med, December 1, 1978; 138(12): 1837 - 1840. [Abstract] [PDF]

				R. Holle, S. B. Levy, and R. A. Stone A Composite Analysis of Renin Classification Methods Arch Intern Med, October 1, 1978; 138(10): 1514 - 1519. [Abstract] [PDF]

				R. Mailman, M. Krigman, R. Mueller, P Mushak, and G. Breese Lead exposure during infancy permanently increases lithium-induced polydipsia Science, August 18, 1978; 201(4356): 637 - 639. [Abstract] [PDF]

				S. Y. Tan, R. H. Noth, and P. J. Mulrow Deoxycorticosterone and 17-Ketosteroids: Elevated Levels in Adult Hypertensive Patients JAMA, July 14, 1978; 240(2): 123 - 126. [Abstract] [PDF]

				M. ESLER, A. ZWEIFLER, O. RANDALL, S. JULIUS, and V. DeQUATTRO The Determinants of Plasma-Renin Activity in Essential Hypertension Ann Intern Med, June 1, 1978; 88(6): 746 - 752. [Abstract] [PDF]

				A. LINDNER, S. W. DOUGLAS, and J. W. ADAMSON Propranolol Effects in Long-Term Hemodialysis Patients with Renin-Dependent Hypertension Ann Intern Med, April 1, 1978; 88(4): 457 - 462. [Abstract] [PDF]

				R. H. McDonald Jr, C. N. Corder, A. H. Vagnucci, and J. Shuman The Multiple Factors Affecting Plasma Renin Activity in Essential Hypertension Arch Intern Med, April 1, 1978; 138(4): 557 - 561. [Abstract] [PDF]

				N. Brautbar, J. Levi, A. Rosler, E. Leitesdorf, M. Djaldeti, M. Epstein, and C. R. Kleeman Familial Hyperkalemia, Hypertension, and Hyporeninemia With Normal Aldosterone Levels: A Tubular Defect in Potassium Handling Arch Intern Med, April 1, 1978; 138(4): 607 - 610. [Abstract] [PDF]

				M. H. Witte, C. L. Witte, S. Jacobs, and R. Kut Peritoneovenous (LeVeen) Shunt: Control of Renin-Aldosterone System in Cirrhotic Ascites JAMA, January 2, 1978; 239(1): 31 - 33. [Abstract] [PDF]

				S. B. LEVY, L. B. TALNER, M. N. COEL, R. HOLLE, and R. A. STONE Renal Vasculature in Essential Hypertension: Racial Differences Ann Intern Med, January 1, 1978; 88(1): 12 - 16. [Abstract] [PDF]

				T. A. Rakowski, W. P. Argy Jr, L. Pierce Jr, and G. E. Schreiner Splenic Cyst Causing Hypertension by Renal Compression JAMA, December 5, 1977; 238(23): 2528 - 2529. [Abstract] [PDF]

				D. A. Nash Jr Hypertension in Polycystic Kidney Disease Without Renal Failure Arch Intern Med, November 1, 1977; 137(11): 1571 - 1575. [Abstract] [PDF]

				P. WEIDMANN, C. BERETTA-PICCOLI, D. HIRSCH, F. C. REUBI, and S. G. MASSRY Curable Hypertension with Unilateral Hydronephrosis: Studies on the Role of Circulating Renin Ann Intern Med, October 1, 1977; 87(4): 437 - 440. [Abstract] [PDF]

				L. S. MARKS, M. H. MAXWELL, and J. J. KAUFMAN Renin, Sodium, and Vasodepressor Response to Saralasin in Renovascular and Essential Hypertension Ann Intern Med, August 1, 1977; 87(2): 176 - 182. [Abstract] [PDF]