Skip to main content
NCBI home page
Current Therapeutic Research, Clinical and Experimental logoLink to Current Therapeutic Research, Clinical and Experimental
. 2008 Dec;69(6):467–479. doi: 10.1016/j.curtheres.2008.12.004

Hemodynamic effect of angiotensin II receptor blockade in postmenopausal women on a high-sodium diet: A double-blind, randomized, placebo-controlled study

Antoinette Pechère-Bertschi 1,*, Marc Maillard 2, Paul Bischof 3, Marc Fathi 4, Michel Burnier 2
PMCID: PMC3969927  PMID: 24692821

Abstract

Background: Hypertension becomes increasingly prevalent after menopause. Postmenopausal women are more responsive to salt than premenopausal women, and they have been reported to develop marked renal vasoconstriction on a high-sodium diet.

Objective: The aim of this study was to assess whether angiotensin II receptor blockade can restore a normal pattern of renal response to salt in postmenopausal women on a high-sodium diet. We also assessed segmental renal sodium handling in that population.

Methods: Normotensive and hypertensive postmenopausal women not receiving hormone replacement therapy were enrolled in this prospective, double-blind, placebo-controlled, crossover study. They were assigned to receive irbesartan 150 mg or placebo for 6 weeks; the sequence in which they received irbesartan or placebo was randomized. During the last week of treatment, they received a high-sodium diet (250 mmol/d). Ambulatory blood pressure (ABP), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF) were measured using sinistrin and para-amino-hippurate clearances. Renal sodium handling was assessed by measuring endogenous lithium clearance on day 7 of the high-salt diet.

Results: Nineteen women (mean age, 54.7 years; range, 43–72 years; 7 normotensive subjects [mean age, 53.4 years; range, 47–61 years] and 12 hypertensive subjects [mean age, 55.4 years; range, 43–72 years]) were included in the study. When the data for all 19 subjects were pooled, ABP was significantly lower with irbesartan than placebo both during the day (120 [3]/79 [2] vs 127 [3]/85 [2] mm Hg; both, P < 0.01) and at night (systolic BP, 107 [4] vs 111 [4] mm Hg [P < 0.01] and diastolic BP, 71 [2] vs 75 [2] mm Hg [P < 0.05]). Compared with placebo, irbesartan was not associated with a significant change in GFR in either the normotensive or the hypertensive women. When the data for all 19 subjects were pooled, irbesartan was associated with a significant increase in ERPF compared with placebo (372 [21] vs324 [18] mL/min · 1.73 m2; P < 0.05). When the hypertensive and normotensive women were considered separately, the effect was more pronounced in the hypertensive women than in the normotensive women, but the changes did not reach statistical significance. When the data for all subjects were pooled, irbesartan was associated with a significant increase in daytime urinary sodium excretion compared with placebo (135 [13] vs 106 [13] μmol/min; P < 0.05) and a significant decrease at night (109 [13] vs 136 [19] μmol/min; P < 0.05). Fractional excretion of lithium (FELi), an inverse marker of proximal sodium reabsorption, increased significantly during the daytime with irbesartan compared with placebo (47% [6.5%] vs 35% [4.7%]; P < 0.05). At nighttime, FELi was significantly higher in the hypertensive subjects receiving irbesartan compared with placebo (43% [7.2%] vs 29% [6.5%]; P < 0.05). The fractional distal reabsorption of sodium did not change significantly with irbesartan compared with placebo.

Conclusions: The results from this study suggest that angiotensin II receptor blockade had a favorable impact on BP, renal hemodynamics, and renal sodium handling in these salt-replete postmenopausal women. Blockade of the renin-angiotensin system restored the normal pattern of renal response to high sodium intake in these women.

Key Words: blood pressure, lithium, renal hemodynamics, gender, angiotensin II receptor blockade

Full Text

The Full Text of this article is available as a PDF (884.5 KB).

References

  • 1.Kannel WB, Hjortland MC, McNamara PM, Gordon T. Menopause and risk of cardiovascular disease: The Framingham study. Ann Intern Med. 1976;85:447–452. doi: 10.7326/0003-4819-85-4-447. [DOI] [PubMed] [Google Scholar]
  • 2.Colditz GA, Willett WC, Stampfer MJ. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987;316:1105–1110. doi: 10.1056/NEJM198704303161801. [DOI] [PubMed] [Google Scholar]
  • 3.Reckelhoff JF, Fortepiani LA. Novel mechanisms responsible for postmenopausal hypertension. Hypertension. 2004;43:918–923. doi: 10.1161/01.HYP.0000124670.03674.15. [DOI] [PubMed] [Google Scholar]
  • 4.Miller JA, Anacta LA, Cattran DC. Impact of gender on the renal response to angiotensin II. Kidney Int. 1999;55:278–285. doi: 10.1046/j.1523-1755.1999.00260.x. [DOI] [PubMed] [Google Scholar]
  • 5.Kang AK, Duncan JA, Cattran DC. Effect of oral contraceptives on the renin angiotensin system and renal function. Am J Physiol Regul Integr Comp Physiol. 2001;280:R807–R813. doi: 10.1152/ajpregu.2001.280.3.R807. [DOI] [PubMed] [Google Scholar]
  • 6.Würzner G, Chiolero A, Maillard M. Renal and neurohormonal responses to increasing levels of lower body negative pressure in men. Kidney Int. 2001;60:1469–1476. doi: 10.1046/j.1523-1755.2001.00950.x. [DOI] [PubMed] [Google Scholar]
  • 7.Pechère-Bertschi A, Maillard M, Stalder H. Renal segmental tubular response to salt during the normal menstrual cycle. Kidney Int. 2002;61:425–431. doi: 10.1046/j.1523-1755.2002.00158.x. [DOI] [PubMed] [Google Scholar]
  • 8.Pechère-Bertschi A, Maillard M, Stalder H. Renal hemodynamic and tubular responses to salt in women using oral contraceptives. Kidney Int. 2003;64:1374–1380. doi: 10.1046/j.1523-1755.2003.00239.x. [DOI] [PubMed] [Google Scholar]
  • 9.Pechère-Bertschi A, Burnier M. Female sex hormones, salt, and blood pressure regulation. Am J Hypertens. 2004;17:994–1001. doi: 10.1016/j.amjhyper.2004.08.009. [DOI] [PubMed] [Google Scholar]
  • 10.Schulman IH, Aranda P, Raij L. Surgical menopause increases salt sensitivity of blood pressure. Hypertension. 2006;47:1168–1174. doi: 10.1161/01.HYP.0000218857.67880.75. [DOI] [PubMed] [Google Scholar]
  • 11.Gosse PLA, Ansoborlo P. Clinical evaluation of the DIASYS integra blood pressure recorder. J Hypertem. 1997;15 18S. [Google Scholar]
  • 12.Magnin JL, Decosterd LA, Centeno C. Determination of trace lithium in biological fluids using graphite furnace atomic absorption spectrophotometry: Variability of urine matrices circumvented by cation exchange solid phase extraction. Pharm Acta Helv. 1996;71:237–246. doi: 10.1016/s0031-6865(96)00020-9. [DOI] [PubMed] [Google Scholar]
  • 13.Steinhäuslin F, Burnier M, Magnin JL. Fractional excretion of trace lithium and uric acid in acute renal failure. J Am Soc Nephrol. 1994;4:1429–1437. doi: 10.1681/ASN.V471429. [DOI] [PubMed] [Google Scholar]
  • 14.Burnier M, Biollaz J, Magnin JL. Renal sodium handling in patients with untreated hypertension and white coat hypertension. Hypertension. 1994;23:496–502. doi: 10.1161/01.hyp.23.4.496. [DOI] [PubMed] [Google Scholar]
  • 15.Polónia J, Diogo D, Caupers P, Damasceno A. Influence of two doses of irbesartan on non-dipper circadian blood pressure rhythm in salt-sensitive black hypertensives under high salt diet. J Cardiovasc Pharmacol. 2003;42:98–104. doi: 10.1097/00005344-200307000-00015. [DOI] [PubMed] [Google Scholar]
  • 16.Reckelhoff JF. Basic research into the mechanisms responsible for postmenopausal hypertension. Int J Clin Pract Suppl. 2004;139:13–19. [PubMed] [Google Scholar]
  • 17.Fortepiani LA, Yanes L, Zhang H. Role of androgens in mediating renal injury in aging SHR. Hypertension. 2003;42:952–955. doi: 10.1161/01.HYP.0000099241.53121.7F. [DOI] [PubMed] [Google Scholar]
  • 18.Reckelhoff JF, Zhang H, Srivastava K. Gender differences in development of hypertension in spontaneously hypertensive rats: Role of the renin-angiotensin system. Hypertension. 2000;35:480–483. doi: 10.1161/01.hyp.35.1.480. [DOI] [PubMed] [Google Scholar]
  • 19.Pechère-Bertschi A, Maillard M, Stalder H. Blood pressure and renal haemodynamic response to salt during the normal menstrual cycle. Clin Sci (Lond) 2000;35:480–483. [PubMed] [Google Scholar]
  • 20.Fortepiani LA, Zhang H, Racusen L. Characterization of an animal model of postmenopausal hypertension in spontaneously hypertensive rats. Hypertension. 2003;41:640–645. doi: 10.1161/01.HYP.0000046924.94886.EF. [DOI] [PubMed] [Google Scholar]
  • 21.Otsuka F, Yamauchi T, Kataoka H. Effects of chronic inhibition of ACE and ATI receptors on glomerular injury in Dahl salt-sensitive rats. Am J Physiol. 1998;274:R1797–R1806. doi: 10.1152/ajpregu.1998.274.6.R1797. [DOI] [PubMed] [Google Scholar]
  • 22.Yoneda H, Toriumi W, Ohmachi Y. Involvement of angiotensin II in development of spontaneous nephrosis in Dahl salt-sensitive rats. Eur J Pharmacol. 1998;362:213–219. doi: 10.1016/s0014-2999(98)00761-4. [DOI] [PubMed] [Google Scholar]
  • 23.Sasaki T, Ohno Y, Otsuka K. Oestrogen attenuates the increases in blood pressure and platelet aggregation in ovariectomized and salt-loaded Dahl salt-sensitive rats. J Hypertem. 2000;18:911–917. doi: 10.1097/00004872-200018070-00013. [DOI] [PubMed] [Google Scholar]
  • 24.Hinojosa-Laborde C, Lange DL, Haywood JR. Role of female sex hormones in the development and reversal of dahl hypertension. Hypertension. 2000;35:484–489. doi: 10.1161/01.hyp.35.1.484. [DOI] [PubMed] [Google Scholar]
  • 25.Quan A, Chakravarty S, Chen JK. Androgens augment proximal tubule transport. Am J Physiol Renal Physiol. 2004;287:F452–F459. doi: 10.1152/ajprenal.00188.2003. [DOI] [PubMed] [Google Scholar]
  • 26.Chiolero A, Maillard M, Nussberger J. Proximal sodium reabsorption: An independent determinant of blood pressure response to salt. Hypertension. 2000;36:631–637. doi: 10.1161/01.hyp.36.4.631. [DOI] [PubMed] [Google Scholar]
  • 27.Burnier M, Bochud M, Maillard M. Proximal tubular function and salt sensitivity. Curr Hypertens Rep. 2006;8:8–15. doi: 10.1007/s11906-006-0035-6. [DOI] [PubMed] [Google Scholar]
  • 28.Burnier M, Hagman M, Nussberger J. Short-term and sustained renal effects of angiotensin II receptor blockade in healthy subjects. Hypertension. 1995;25:602–609. doi: 10.1161/01.hyp.25.4.602. [DOI] [PubMed] [Google Scholar]
  • 29.Falconnet C, Bochud M, Bovet P. Gender difference in the response to an angiotensin-converting enzyme inhibitor and a diuretic in hypertensive patients of African descent. J Hypertens. 2004;22:1213–1220. doi: 10.1097/00004872-200406000-00023. [DOI] [PubMed] [Google Scholar]

Articles from Current Therapeutic Research, Clinical and Experimental are provided here courtesy of Elsevier

RESOURCES