Increased Aldosterone/Renin Quotient in Obese Hypertensive Women: A Novel Role for Low-density Lipoproteins?

Abstract

Obesity, especially visceral obesity, is strongly associated with arterial hypertension. Indeed, obesity hypertension has to be considered as the most common form of essential hypertension. However, the exact nature of the relationship between obesity and increased blood pressure remains poorly understood. Involvement of renin-independent mechanisms has been suggested in adrenal stimulation of aldosterone secretion in obese patients. This investigation examined the plasma levels of renin, aldosterone, insulin, and HDL and LDL in obese hypertensive and obese normotensive women. The group of hypertensive obese women showed significantly reduced plasma levels of renin and increased aldosterone/renin quotient (ARQ) compared to obese normotensive women. Plasma aldosterone levels were not significantly different between hypertensive and normotensive obese women. In addition, plasma levels of LDL-cholesterol in the hypertensive obese group were significantly increased in comparison to the obese normotensive group. No differences were observed in HDL-cholesterol or total cholesterol/HDL-C ratios between the two groups. We therefore examined the effect of LDL on angiotensin II-stimulated aldosterone release from human adrenocortical H295R cells. Treatment of adrenocortical cells with LDL led to a sensitization towards stimulation by angiotensin II, dramatically increasing angiotensin II-induced aldosterone production, so the increased aldosterone/renin ratio observed in the hypertensive group may be due to the enhanced LDL levels in these patients and/or other adipocyte-derived mineralocorticoid-stimulating factors.

Obesity - hypertension - aldosterone - LDL-cholesterol

References

• 1 Kopelman PG. Obesity as a medical problem.  Nature. 2000;  404 635-643
• 2 Sharabi Y, Grotto I, Huerta M, Grossman E. Susceptibility of the influence of weight on blood pressure in men versus women: lessons from a large-scale study of young adults.  Am J Hypertens. 2004;  17 404-408
• 3 Jones DW, Kim JS, Andrew ME, Kim SJ, Hong YP. Body mass index and blood pressure in Korean men and women: the Korean National Blood Pressure Survey.  J Hypertens. 1994;  12 1433-1437
• 4 Garrison RJ, Kannel WB, Stokes III J, Castelli WP. Incidence and precursors of hypertension in young adults: the Framingham Offspring Study.  Prev Med. 1987;  16 235-251
• 5 Lamounier-Zepter V, Bornstein SR, Ehrhart-Bornstein M. Mechanisms of obesity-related hypertension.  Horm Metab Res. 2004;  36 376-380
• 6 Freel EM, Connell JM. Mechanisms of hypertension: the expanding role of aldosterone.  J Am Soc Nephrol. 2004;  15 1993-2001
• 7 Stewart PM. Mineralocorticoid hypertension.  Lancet. 1999;  353 1341-1347
• 8 Thakur V, Richards R, Reisin E. Obesity, hypertension, and the heart.  Am J Med Sci. 2001;  321 242-248
• 9 Egan BM, Stepniakowski K, Goodfriend TL. Renin and aldosterone are higher and the hyperinsulinemic effect of salt restriction greater in subjects with risk factors clustering.  Am J Hypertens. 1994;  7 886-893
• 10 Licata G, Scaglione R, Ganguzza A. et al. . Central obesity and hypertension. Relationship between fasting serum insulin, plasma renin activity, and diastolic blood pressure in young obese subjects.  Am J Hypertens. 1994;  7 314-320
• 11 Goodfriend TL, Egan BM, Kelley DE. Aldosterone in obesity.  Endocr Res. 1998;  24 789-796
• 12 Rocchini AP, Katch VL, Grekin R, Moorehead C, Anderson J. Role for aldosterone in blood pressure regulation of obese adolescents.  Am J Cardiol. 1986;  57 613-618
• 13 El Gharbawy AH, Nadig VS, Kotchen JM. et al. . Arterial pressure, left ventricular mass, and aldosterone in essential hypertension.  Hypertension. 2001;  37 845-850
• 14 Goodfriend TL, Kelley DE, Goodpaster BH, Winters SJ. Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women.  Obes Res. 1999;  7 355-362
• 15 de Paula RB, da Silva AA, Hall JE. Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration.  Hypertension. 2004;  43 41-47
• 16 Harp JB, Henry SA, DiGirolamo M. Dietary weight loss decreases serum angiotensin-converting enzyme activity in obese adults.  Obes Res. 2002;  10 985-990
• 17 Cooper R, Forrester T, Ogunbiyi O, Muffinda J. Angiotensinogen levels and obesity in four black populations. ICSHIB Investigators.  J Hypertens. 1998;  16 571-575
• 18 Engeli S, Bohnke J, Gorzelniak K. et al. . Weight loss and the renin-angiotensin-aldosterone system.  Hypertension. 2005;  45 356-362
• 19 Weber MA, Smith DH, Neutel JM. Differing roles of body mass and the renin-angiotensin system in mediating the hypertension syndrome.  Am J Nephrol. 2000;  20 169-174
• 20 Pietzsch J, Subat S, Nitzsche S, Leonhardt W, Schentke KU, Hanefeld M. Very fast ultracentrifugation of serum lipoproteins: influence on lipoprotein separation and composition.  Biochim Biophys Acta. 1995;  1254 77-88
• 21 Goodfriend TL, Ball DL, Gardner HW. An oxidized derivative of linoleic acid affects aldosterone secretion by adrenal cells in vitro.  Prostaglandins Leukot Essent Fatty Acids. 2002;  67 163-167
• 22 Goodfriend TL, Ball DL, Egan BM, Campbell WB, Nithipatikom K. Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion.  Hypertension. 2004;  43 358-363
• 23 Ehrhart-Bornstein M, Hinson JP, Bornstein SR, Scherbaum WA, Vinson GP. Intraadrenal interactions in the regulation of adrenocortical steroidogenesis.  Endocr Rev. 1998;  19 101-143
• 24 Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A. et al. . Human adipocytes secrete mineralocorticoid releasing factors.  Proc Natl Acad Sci USA. 2003;  100 14211-14216
• 25 Ehrhart-Bornstein M, Arakelyan K, Krug AW, Scherbaum WA, Bornstein SR. Fat cells may be the obesity-hypertension link: human adipogenic factors stimulate aldosterone secretion from adrenocortical cells.  Endocr Res. 2004;  30 865-870
• 26 Lamounier-Zepter V, Ehrhart-Bornstein M, Bornstein SR. Mineralocorticoid-stimulating activity of adipose tissue.  Best Pract Res Clin Endocrinol Metab. 2005;  19 567-575
• 27 Kovanen PT, Faust JR, Brown MS, Goldstein JL. Low density lipoprotein receptors in bovine adrenal cortex. I. Receptor-mediated uptake of low density lipoprotein and utilization of its cholesterol for steroid synthesis in cultured adrenocortical cells.  Endocrinology. 1979;  104 599-609
• 28 Carr BR, Simpson ER. Lipoprotein utilization and cholesterol synthesis by the human fetal adrenal gland.  Endocr Rev. 1981;  2 306-326
• 29 van der Linde NA, Sijbrands EJ, Boomsma F, van den Meiracker AH. Effect of low-density lipoprotein cholesterol on angiotensin II sensitivity.  A randomized trial with fluvastatin. Hypertension. 2006;  17 , (Epub ahead of print).

Correspondence