Low-Renin Essential Hypertension: Diminution of Aldosterone Suppression?

  • Thomas A. Wilson
  • Robert M. Carey
Conference paper


Renin profiling of hypertensive patients has led to the identification of a subgroup of patients with low-basal plasma renin activity (PRA) that does not increase in response to various maneuvers known to stimulate PRA in normal individuals. A small percentage of these individuals subsequently is found to have primary aldosteronism or glucocorticoid-suppressible hypertension, but the majority have normal plasma aldosterone concentrations. Despite differences in the methods of ascertainment of PRA and the stimuli applied to induce renin release, as well as difficulties in obtaining controls that are appropriately matched for age, sex, and race (1, 2), most investigators have identified suppressed PRA in 17%—46% of patients with essential hypertension (3). Yet, despite its prevalence, the pathophysiology of low- renin essential hypertension (LREH) remains obscure. In this paper, we will attempt to summarize what is known about LREH, particularly with respect to adrenal function, and propose a hypothesis of the pathophysiology involved.


Essential Hypertension Plasma Renin Activity Primary Aldosteronism Aldosterone Secretion Adrenal Vein Sampling 
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  1. 1.
    Dunn MH, Tannen RL (1974) Low renin hypertension. Kidney Int 5: 317–325PubMedCrossRefGoogle Scholar
  2. 2.
    Noth RH (1978) Interpretation of plasma renin activity. Arch Intern Med 138: 528–529PubMedCrossRefGoogle Scholar
  3. 3.
    Kaplan NM (1978) Clinical hypertension. Williams & Wilkins, Baltimore, Md, pp 287–304Google Scholar
  4. 4.
    Carey RM, Douglas JG, Schweikert JR, Liddle GW (1972) The syndrome of essential hypertension and suppressed plasma renin activity: Normalization of blood pressure with spironolactone. Arch Intern Med 130: 849–854PubMedCrossRefGoogle Scholar
  5. 5.
    Crane MG, Harris JJ, Johns VJ (1972) Hyporeninemic hypertension. Am J Med 52: 457–466PubMedCrossRefGoogle Scholar
  6. 6.
    Adlin EV, Marks AD, Channick BJ (1972) Spironolactone and hydrochlorothiazide in essential hypertension. Arch Intern Med 130: 855–858PubMedCrossRefGoogle Scholar
  7. 7.
    McDonald RH, Corder CN, Vagnucci AH, Shuman J (1978) The multiple functions affecting plasma renin activity in essential hypertension. Arch Intern Med 138: 557–561PubMedCrossRefGoogle Scholar
  8. 8.
    Padfield PL, Brown JJ, Lever AF, Schalekamp MAD, Beevers DG, Davies DL, Robertson JIS, Tree M, Titterington M (1975) Is low renin hypertension a stage in the development of essential hypertension of a diagnostic entity? Lancet 1: 548–550PubMedCrossRefGoogle Scholar
  9. 9.
    Esler M, Zweifler A, Randall O, Julius S, DeQuattro V (1978) The determinants of plasma renin activity in essential hypertension. Ann Intern Med 88: 746–752PubMedGoogle Scholar
  10. 10.
    Lowder SC, Humet P, Liddle GW (1976) Contrasting effects of hypoglycemia on plasma renin activity and cyclic adenosine 3′5′ monophosphate (cyclic AMP) in essential hypertension. Circ Res 38: 105–108PubMedGoogle Scholar
  11. 11.
    Jose A, Crout JR, Kaplan NM (1970) Suppressed plasma renin activity in essential hypertension: Roles of plasma volume, blood pressure, and sympathetic nervous system. Ann Intern Med 72: 9–16PubMedGoogle Scholar
  12. 12.
    Mitchell JR, Taylor AH, Pool JL, Lake CR, Rollins DE, Bartter FC (1977) Renin-aldosterone profiling in hypertension. Ann Intern Med 87: 596PubMedGoogle Scholar
  13. 13.
    Vaughan ED, Laragh JH, Gavras I, Bühler FR, Gavras H, Brunner HR, Baer L (1974) The volume factor in low and normal renin essential hypertension: Its treatment with either spironolactone or chlorthalidone. In: Laragh JH (ed) Hypertension manual. Yorke Medical Group, New York, pp 851–871Google Scholar
  14. 14.
    Swales JO (1975) Low renin hypertension: Nephrosclerosis? Lancet 1: 75–77PubMedCrossRefGoogle Scholar
  15. 15.
    Woods JW, Liddle GW, Stant EG, Michelakis AM, Brill AB (1969) Effect of an adrenal inhibitor in hypertensive patients with suppressed renin. Arch Intern Med 123: 366–370PubMedCrossRefGoogle Scholar
  16. 16.
    Julius S, Esler M (1976) Increased central blood volume: A possible pathological factor in mild low-renin essential hypertension. Clin Sci Mol Med 51: 207S–210SGoogle Scholar
  17. 17.
    Lebel S, Schalekamp MA, Beevers DG, Brown JJ, Davies DL, Fraser R, Kremer D, Lever AF, Morton JJ, Robertson JIS, Tree M, Wilson A (1974) Sodium and renin-angiotensin system in essential hypertension and mineralocorticoid excess. Lancet 2: 308–310PubMedCrossRefGoogle Scholar
  18. 18.
    Schalekamp MA, Lebel M, Beevers DG, Fraser R, Kolsters G, Birkenhäger WH (1974) Body fluid volume in low renin hypertension. Lancet 2: 310–311PubMedCrossRefGoogle Scholar
  19. 19.
    Krakoff LR, Goodwin FJ, Baer L, Torres M, Laragh JH (1970) The role of renin in the exaggerated natriuresis of hypertension. Circulation 42: 335–345PubMedGoogle Scholar
  20. 20.
    Luft FC, Grim CE, Willis LR, Higgins JT, Weinberger MH (1977) Natriuretic response to saline infusion in normotensive and hypertensive man: The role of renin suppression in exaggerated natriuresis. Circulation 55: 779–784PubMedGoogle Scholar
  21. 21.
    Douglas JG, Hollifield JW, Liddle GW (1974) Treatment of low renin essential hypertension: Comparison of spironolactone and a hydrochlorothiazide-triamterene combination. JAMA 227: 518–521PubMedCrossRefGoogle Scholar
  22. 22.
    Sekihara H, Hollifield JW, Island DP, Slaton PE, Liddle GW (1979) Evidence for heterogeneity of mineralocorticoids in urine of patients with low renin essential hypertension. J Clin Endocrinol Metab 48: 143–147PubMedCrossRefGoogle Scholar
  23. 23.
    Tan S Y, Mulrow PJ (1979) Low renin essential hypertension: Failure to demonstrate excess 11-deoxycorticosterone production. J Clin Endocrinol Metab 49: 790–793PubMedCrossRefGoogle Scholar
  24. 24.
    Taylor AA, Mitchell JR, Bartter FC, Snodgrass WR, McMurty RJ, Gill JR, Franklin RB (1978) Effect of aminoglutethimide on blood pressure and steroid secretion in patients with low renin essential hypertension. J Clin Invest 62: 162–168PubMedCrossRefGoogle Scholar
  25. 25.
    Baxter JD, Schambelan M, Matulich DT, Spinder BJ, Taylor AA, Bartter FC (1976) Aldosterone receptors and the evaluation of plasma mineralocorti- coid activity in normal and hypertensive states. J Clin Invest 58: 579–589PubMedCrossRefGoogle Scholar
  26. 26.
    Liddle GW, Hollifield JW, Slaton RE, Wilson HM (1976) Effects of various adrenal inhibitors in low renin essential hypertension. J Steroid Biochem 7: 937–940PubMedCrossRefGoogle Scholar
  27. 27.
    Wisgerhof M, Brown RD (1978) Increased adrenal sensitivity to angiotensin II in low-renin essential hypertension. J Clin Invest 61: 1456–1462PubMedCrossRefGoogle Scholar
  28. 28.
    Marks AD, Marks DB, Kanefsky TM, Adlin VE, Channick BJ (1979) Enhanced adrenal responsiveness to angiotensin II in patients with low renin essential hypertension. J Clin Endocrinol Metab 48: 266–270PubMedCrossRefGoogle Scholar
  29. 29.
    Marks AD, Marks DB, Kim YM, Moctezuma J, Adlin EV, Channick BJ (1978) The pressor responses to angiotensin II in patients with low renin essential hypertension. Circ Res 42: 864–869PubMedGoogle Scholar
  30. 30.
    Rifai A, Beierwaltes WH, Freitas JE, Grekin R (1978) Adrenal scintigraphy in low renin essential hypertension. Clin Nucl Med 3: 282–286PubMedCrossRefGoogle Scholar
  31. 31.
    Gunnells JC, McGuffin WL, Robinson RR, Grim CE, Wells S, Silver D, Glenn JF (1970) Hypertension, adrenal abnormalities and alterations in plasma renin activity. Ann Intern Med 73: 901–911PubMedGoogle Scholar
  32. 32.
    Grim CE, Esterly JA, Lungo DL, Keitzer WF (1974) “Inappropriate” production of aldosterone associated with adrenal hyperplasia (abstr). Endocrinology 94(Suppl): A243Google Scholar
  33. 33.
    Grim CE (1975) Low renin “essential” hypertension: A variant of classic aldosteronism? Arch Intern Med 135: 347–350PubMedCrossRefGoogle Scholar
  34. 34.
    Genest J, Nowaczynski W, Kuchel O, Messerli F, Boucher R, Rojo-Ortega M (1975) Mineralocorticoid activity in patients in the early benign phase of essential hypertension. J Steroid Biochem 6: 755–760PubMedCrossRefGoogle Scholar
  35. 35.
    Beevers DG, Morton JJ, Nelson CS, Padfield PL, Tittenington M, Tree M (1977) Angiotensin II in essential hypertension. Br Med J 1: 415PubMedCrossRefGoogle Scholar
  36. 36.
    Mantero F, Opocher G, Armanini D, Boscaro M, Edwards CRW (1979) Effect of serotonin (5-HT) on plasma aldosterone in man (abstr). Acta Endocrinol [Suppl] (Copenh) 225S: 345Google Scholar
  37. 37.
    Haning R, Tait SAS, Tait JF (1970) In vitro effects of ACTH, angiotensins, serotonin and potassium on steroid output and conversion of corticosterone to aldosterone by isolated adrenal cells. Endocrinology 87: 1147–1167PubMedCrossRefGoogle Scholar
  38. 38.
    Liddle GW (1975) Is hypertension essential? Trans Assoc Am Physicians 88: 55–69PubMedGoogle Scholar
  39. 39.
    Collins RD, Weinberger MH, Dowdy AJ, Nokes GW, Gonzales CM, Luetscher JA (1970) Abnormally sustained aldosterone secretion during salt loading in patients with various forms of benign hypertension: Relation to plasma renin activity. J Clin Invest 49: 1415–1426Google Scholar
  40. 40.
    Gross MD, Gniadek TC, Grekin RJ (1980) Inhibition of aldosterone secretion by cyproheptadine in primary aldosteronism due to bilateral hyperplasia. Clin Res 28: 260AGoogle Scholar
  41. 41.
    Carey RM, Thorner MO, Ortt EM (1979) Effects of metoclopramide and bromocriptine on the renin-angiotensin-aldosterone system in man: Dopaminergic control of aldosterone. J Clin Invest 63: 727–735Google Scholar
  42. 42.
    McKenna TJ, Island DP, Nicholson WE, Liddle GW (1979) Dopamine inhibits angiotensin-stimulated aldosterone biosynthesis in bovine adrenal cells. J Clin Invest 64: 787–791CrossRefGoogle Scholar
  43. 43.
    Goldberg LI (1972) Cardiovascular and renal actions of dopamine: Potential clinical applications. Pharmacol Rev 24: 1–27PubMedGoogle Scholar
  44. 44.
    Carey RM, VanLoon GR, Baines AD, Ortt EM (submitted) Plasma and urinary dopamine during dietary sodium depletion in man: Evidence for decreased dopaminergic activityGoogle Scholar
  45. 45.
    Cuche JC, Kuchel O, Barbeau A, Boucher R, Genest J (1972) Relationship between the adrenergic nervous system and renin during adaptation to upright posture: A possible role for 3,4 dihydroxyphe- nylethylamine (dopamine). Clin Sci 43: 481–491PubMedGoogle Scholar
  46. 46.
    Goldberg LI, Volkman PH, Kohli JD (1978) A comparison of the vascular dopamine receptor with other dopamine receptors. Annu Rev Pharmacol Toxicol 18: 57–79PubMedCrossRefGoogle Scholar
  47. 47.
    Ziegler MG, Lake CR, Williams AC, Teychenne PF, Shoulson I, Steinsland O (1979) Bromocriptine inhibits norepinephrine release. Clin Pharmacol Ther 25: 137–142PubMedGoogle Scholar
  48. 48.
    Kollock R, Kobayashi K, DeQuattro V (1981) Evidence in primary hypertension. Hypertension (in press)Google Scholar
  49. 49.
    Esler M, Zweifler A, Randall O, Julius S, Bennett J, Rydelek P, Cohen E, DeQuattro V (1976) Suppression of sympathetic nervous functions in low-renin essential hypertension. Lancet 2: 115–118PubMedCrossRefGoogle Scholar
  50. 50.
    Carey R, Thorner MO, Orth EM (1981) Dopaminergic inhibition of metoclopramide-induced aldosterone secretion in man: Dissociation of responses to dopamine and bromocriptine, J clin Invest (in press)Google Scholar
  51. 51.
    Volkman PH, Goldberg LI (1976) Lack of correlation between inhibition of prolactin release and stimulation of dopaminergic renal vasodilation. Pharm 18: 130Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1981

Authors and Affiliations

  • Thomas A. Wilson
  • Robert M. Carey

There are no affiliations available

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