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. 1978 Jun;61(6):1456–1462. doi: 10.1172/JCI109065

Increased Adrenal Sensitivity to Angiotensin II in Low-Renin Essential Hypertension

Max Wisgerhof 1, Ronald D Brown 1
PMCID: PMC372671  PMID: 659608

Abstract

Studies were undertaken to determine if the dissociation of aldosterone and plasma renin activity in low-renin essential hypertension is due to altered adrenal responsiveness to angiotensin II. The responsiveness of the adrenal glands to angiotensin II was determined by infusing graded doses of angiotensin II into normal subjects and into patients with essential hypertension and measuring changes in levels of plasma aldosterone in response to the infusion. To minimize the influence of endogenous angiotensin II and ACTH, supplemental sodium and dexamethasone were given before the infusions. Levels of plasma aldosterone and plasma renin activity were determined in normal subjects and in the same patients after the combined stimuli of furosemide and upright posture, a maneuver used to increase the level of endogenous angiotensin II. To determine if the changes in levels of plasma aldosterone during infusion of angiotensin II were due to alteration of the metabolic clearance of aldosterone, the metabolic clearance of aldosterone was measured before and during the infusion of angiotensin II.

After sodium loading, dexamethasone treatment, and supine posture, levels of plasma aldosterone of normal subjects and patients with essential hypertension were suppressed equally. In response to the infusion of angiotensin II, the levels of plasma aldosterone of patients with low-renin essential hypertension were significantly higher than those of normal subjects or of patients with normal-renin essential hypertension. After furosemide and upright posture, levels of plasma aldosterone of patients with low-renin essential hypertension were significantly higher than those of patients with normal-renin essential hypertension, despite a blunted response in plasma renin activity of the patients with low-renin essential hypertension. Decreases in metabolic clearance of aldosterone during infusion of angiotensin II were similar in patients with normal-renin essential hypertension and in patients with low-renin essential hypertension and accounted for only a small fraction of the marked increase in levels of plasma aldosterone of patients with low-renin essential hypertension. It is concluded that patients with low-renin essential hypertension have increased adrenal sensitivity to angiotensin II. This increased sensitivity may explain the dissociation of aldosterone and plasma renin activity in low-renin essential hypertension.

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Selected References

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  1. Bayard F., Alicandri C. L., Beitins I. Z., Lubash G. D., Kowarski A., Migeon C. J. A dynamic study of plasma renin activity and aldosterone concentration in normal and hypertensive subjects. Metabolism. 1971 May;20(5):513–519. doi: 10.1016/0026-0495(71)90126-0. [DOI] [PubMed] [Google Scholar]
  2. Brown R. D. Aldosterone metabolic clearance is normal in low-renin essential hypertension. J Clin Endocrinol Metab. 1976 Apr;42(4):661–666. doi: 10.1210/jcem-42-4-661. [DOI] [PubMed] [Google Scholar]
  3. Cannon P. J., Ames R. P., Laragh J. H. Relation between potassium balance and aldosterone secretion in normal subjects and in patients with hypertensive or renal tubular disease. J Clin Invest. 1966 Jun;45(6):865–879. doi: 10.1172/JCI105402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carey R. M., Douglas J. G., Schweikert J. R., Liddle G. W. The syndrome of essential hypertension and suppressed plasma renin activity. Normalization of blood pressure with spironolactone. Arch Intern Med. 1972 Dec;130(6):849–854. [PubMed] [Google Scholar]
  5. Collins R. D., Weinberger M. H., Dowdy A. J., Nokes G. W., Gonzales C. M., Luetscher J. A. Abnormally sustained aldosterone secretion during salt loading in patients with various forms of benign hypertension; relation to plasma renin activity. J Clin Invest. 1970 Jul;49(7):1415–1426. doi: 10.1172/JCI106359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crane M. G., Harris J. J. Effect of aging on renin activity and aldosterone excretion. J Lab Clin Med. 1976 Jun;87(6):947–959. [PubMed] [Google Scholar]
  7. Fishman L. M., Küchel O., Liddle G. W., Michelakis A. M., Gordon R. D., Chick W. T. Incidence of primary aldosteronism uncomplicated "essential" hypertension. A prospective study with elevated aldosterone secretion and suppressed plasma renin activity used as diagnostic criteria. JAMA. 1968 Aug 12;205(7):497–502. doi: 10.1001/jama.205.7.497. [DOI] [PubMed] [Google Scholar]
  8. Grim C., Winnacker J., Peters T., Gilbert G. Low renin, "normal" aldosterone and hypertension: circadian rhythm of renin, aldosterone, cortisol and growth hormone. J Clin Endocrinol Metab. 1974 Aug;39(2):247–256. doi: 10.1210/jcem-39-2-247. [DOI] [PubMed] [Google Scholar]
  9. Haber E., Koerner T., Page L. B., Kliman B., Purnode A. Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects. J Clin Endocrinol Metab. 1969 Oct;29(10):1349–1355. doi: 10.1210/jcem-29-10-1349. [DOI] [PubMed] [Google Scholar]
  10. Himathongkam T., Dluhy R. G., Williams G. H. Potassim-aldosterone-renin interrelationships. J Clin Endocrinol Metab. 1975 Jul;41(1):153–159. doi: 10.1210/jcem-41-1-153. [DOI] [PubMed] [Google Scholar]
  11. Hollenberg N. K., Chenitz W. R., Adams D. F., Williams G. H. Reciprocal influence of salt intake on adrenal glomerulosa and renal vascular responses to angiotensin II in normal man. J Clin Invest. 1974 Jul;54(1):34–42. doi: 10.1172/JCI107748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kisch E. S., Dluhy R. G., Williams G. H. Enhanced aldosterone response to angiotensin II in human hypertension. Circ Res. 1976 Jun;38(6):502–505. doi: 10.1161/01.res.38.6.502. [DOI] [PubMed] [Google Scholar]
  13. Lowder S. C., Liddle G. W. Prolonged alteration of renin responsiveness after spironolactone therapy. A cause of false-negative testing for low-renin hypertension. N Engl J Med. 1974 Dec 5;291(23):1243–1244. doi: 10.1056/NEJM197412052912309. [DOI] [PubMed] [Google Scholar]
  14. Luetscher J. A., Weinberger M. H., Dowdy A. J., Nokes G. W., Balikian H., Brodie A., Willoughby S. Effects of sodium loading, sodium depletion and posture on plasma aldosterone concentration and renin activity in hypertensive patients. J Clin Endocrinol Metab. 1969 Oct;29(10):1310–1318. doi: 10.1210/jcem-29-10-1310. [DOI] [PubMed] [Google Scholar]
  15. MATTINGLY D. A simple fluorimetric method for the estimation of free 11-hydroxycorticoids in human plasma. J Clin Pathol. 1962 Jul;15:374–379. doi: 10.1136/jcp.15.4.374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McKenzie J. K., Clements J. A. Simplified radioimmunoassay for serum aldosterone utilizing increased antibody specificity. J Clin Endocrinol Metab. 1974 Apr;38(4):622–627. doi: 10.1210/jcem-38-4-622. [DOI] [PubMed] [Google Scholar]
  17. Mendelsohn F. A., Johnston C. I., Doyle A. E., Scoggins B. A., Denton D. A., Coghlan J. P. Renin, angiotensin II, and adrenal corticosteroid relationships during sodium deprivation and angiotensin infusion in normotensive and hypertensive man. Circ Res. 1972 Nov;31(5):728–739. doi: 10.1161/01.res.31.5.728. [DOI] [PubMed] [Google Scholar]
  18. Messerli F. H., Nowaczynski W., Honda M., Genest J., Boucher R., Kuchel O., Rojo-Ortega J. M. Effects of angiotensin II on steroid metabolism and hepatic blood flow in man. Circ Res. 1977 Feb;40(2):204–207. doi: 10.1161/01.res.40.2.204. [DOI] [PubMed] [Google Scholar]
  19. Rayyis S. S., Horton R. Effect of angiotensin II on adrenal and pituitary function in man. J Clin Endocrinol Metab. 1971 Apr;32(4):539–546. doi: 10.1210/jcem-32-4-539. [DOI] [PubMed] [Google Scholar]
  20. TAIT J. F., LITTLE B., TAIT S. A., FLOOD C. The metabolic clearance rate of aldosterone in pregnant and nonpregnant subjects estimated by both single-injection and constant-infusion methods. J Clin Invest. 1962 Dec;41:2093–2100. doi: 10.1172/JCI104667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Weinberger M. H., Dowdy A. J., Nokes G. W., Luetscher J. A. Plasma renin activity and aldosterone secretion in hypertensive patients during high and low sodium intake and administration of diuretic. J Clin Endocrinol Metab. 1968 Mar;28(3):359–371. doi: 10.1210/jcem-28-3-359. [DOI] [PubMed] [Google Scholar]
  22. Woods J. W., Liddle G. W., Michelakis A. M., Brill A. B. Effect of an adrenal inhibitor in hypertensive patients with suppressed renin. Arch Intern Med. 1969 Apr;123(4):366–370. [PubMed] [Google Scholar]

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