901
Views
156
CrossRef citations to date
0
Altmetric
Review

Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics

&
Pages 793-802 | Published online: 10 Jan 2014

References

  • Lloyd-Jones D, Adams R, Carnethon M et al. Heart disease and stroke statistics – 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation119(3), 480–486 (2009).
  • Chobanian AV, Bakris GL, Black HR et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension42(6), 1206–1252 (2003).
  • Ellison DH, Velazquez H, Wright FS. Thiazide-sensitive sodium chloride cotransport in early distal tubule. Am. J. Physiol.253(3 Pt 2), F546–F554 (1987).
  • Bachmann S, Velazquez H, Obermuller N, Reilly RF, Moser D, Ellison DH. Expression of the thiazide-sensitive Na–Cl cotransporter by rabbit distal convoluted tubule cells. J. Clin. Invest.96(5), 2510–2514 (1995).
  • Obermuller N, Bernstein P, Velazquez H et al. Expression of the thiazide-sensitive Na–Cl cotransporter in rat and human kidney. Am. J. Physiol.269(6 Pt 2), F900–F910 (1995).
  • Adrogue HJ, Madias NE. Sodium and potassium in the pathogenesis of hypertension. N. Engl. J. Med.356(19), 1966–1978 (2007).
  • Conway J, Lauwers P. Hemodynamic and hypotensive effects of long-term therapy with chlorothiazide. Circulation21, 21–27 (1960).
  • van Brummelen P, Man in ‘t Veld AJ, Schalekamp MA. Hemodynamic changes during long-term thiazide treatment of essential hypertension in responders and nonresponders. Clin. Pharmacol. Ther.27(3), 328–336 (1980).
  • Lake CR, Ziegler MG, Coleman MD, Kopin IJ. Hydrochlorothiazide-induced sympathetic hyperactivity in hypertensive patients. Clin. Pharmacol. Ther.26(4), 428–432 (1979).
  • Wilson IM, Freis ED. Relationship between plasma and extracellular fluid volume depletion and the antihypertensive effect of chlorothiazide. Circulation20, 1028–1036 (1959).
  • Tarazi RC, Dustan HP, Frohlich ED. Long-term thiazide therapy in essential hypertension. Evidence for persistent alteration in plasma volume and renin activity. Circulation41(4), 709–717 (1970).
  • Winer BM. The antihypertensive actions of benzothiadiazines. Circulation23, 211–218 (1961).
  • Anderson J, Godfrey BE, Hill DM, Munro-Faure AD, Sheldon J. A comparison of the effects of hydrochlorothiazide and of frusemide in the treatment of hypertensive patients. Q. J. Med.40(160), 541–560 (1971).
  • Holland OB, Gomez-Sanchez CE, Kuhnert LV, Poindexter C, Pak CY. Antihypertensive comparison of furosemide with hydrochlorothiazide for black patients. Arch. Intern. Med.139(9), 1015–1021 (1979).
  • Hughes AD. How do thiazide and thiazide-like diuretics lower blood pressure? J. Renin Angiotensin Aldosterone Syst.5(4), 155–160 (2004).
  • Shah S, Khatri I, Freis ED. Mechanism of antihypertensive effect of thiazide diuretics. Am. Heart J.95(5), 611–618 (1978).
  • Aleksandrow D, Wysznacka W, Gajewski J. Influence of chlorothiazide upon arterial responsiveness to nor-epinephrine in hypertensive subjects. N. Engl. J. Med.261, 1052–1055 (1959).
  • Freis ED, Wanko A, Schnaper HW, Frohlich ED. Mechanism of the altered blood pressure responsiveness produced by chlorothiazide. J. Clin. Invest.39, 1277–1281 (1960).
  • Colas B, Slama M, Collin T, Safar M, Andrejak M. Mechanisms of methyclothiazide-induced inhibition of contractile responses in rat aorta. Eur. J. Pharmacol.408(1), 63–67 (2000).
  • Calder JA, Schachter M, Sever PS. Direct vascular actions of hydrochlorothiazide and indapamide in isolated small vessels. Eur. J. Pharmacol.220(1), 19–26 (1992).
  • Calder JA, Schachter M, Sever PS. Potassium channel opening properties of thiazide diuretics in isolated guinea pig resistance arteries. J. Cardiovasc. Pharmacol.24(1), 158–164 (1994).
  • Pickkers P, Hughes AD, Russel FG, Thien T, Smits P. Thiazide-induced vasodilation in humans is mediated by potassium channel activation. Hypertension32(6), 1071–1076 (1998).
  • Beermann B, Groschinsky-Grind M. Pharmacokinetics of hydrochlorothiazide in man. Eur. J. Clin. Pharmacol.12(4), 297–303 (1977).
  • Niemeyer C, Hasenfuss G, Wais U, Knauf H, Schafer-Korting M, Mutschler E. Pharmacokinetics of hydrochlorothiazide in relation to renal function. Eur J. Clin. Pharmacol.24(5), 661–665 (1983).
  • Kreeft JH, Langlois S, Ogilvie RI. Comparative trial of indapamide and hydrochlorothiazide in essential hypertension, with forearm plethysmography. J. Cardiovasc. Pharmacol.6(4), 622–626 (1984).
  • Pickkers P, Russel FG, Hughes AD, Thien T, Smits P. Hydrochlorothiazide exerts no direct vasoactivity in the human forearm. J. Hypertens.13(12 Pt 2), 1833–1836 (1995).
  • Pickkers P, Garcha RS, Schachter M, Smits P, Hughes AD. Inhibition of carbonic anhydrase accounts for the direct vascular effects of hydrochlorothiazide. Hypertension33(4), 1043–1048 (1999).
  • Mironneau J, Savineau JP, Mironneau C. Compared effects of indapamide, hydrochlorothiazide and chlorthalidone on electrical and mechanical activities in vascular smooth muscle. Eur. J. Pharmacol.75(2–3), 109–113 (1981).
  • Del Rio M, Chulia T, Gonzalez P, Tejerina T. Effects of indapamide on contractile responses and 45Ca2+ movements in various isolated blood vessels. Eur. J. Pharmacol.250(1), 133–139 (1993).
  • Abrahams Z, Tan LL, Pang MY, Abrahams B, Tan MM, Wright JM. Demonstration of an in vitro direct vascular relaxant effect of diuretics in the presence of plasma. J. Hypertens.14(3), 381–388 (1996).
  • Abrahams Z, Pang MY, Lam EK, Wright JM. What is the plasma cofactor required by diuretics for direct vascular relaxant effect in vitro? J. Hypertens.16(6), 801–809 (1998).
  • Zhu Z, Zhu S, Liu D, Cao T, Wang L, Tepel M. Thiazide-like diuretics attenuate agonist-induced vasoconstriction by calcium desensitization linked to Rho kinase. Hypertension45(2), 233–239 (2005).
  • Tobian L. Why do thiazide diuretics lower blood pressure in essential hypertension? Annu. Rev. Pharmacol.7, 399–408 (1967).
  • Bennett WM, McDonald WJ, Kuehnel E, Hartnett MN, Porter GA. Do diuretics have antihypertensive properties independent of natriuresis? Clin. Pharmacol. Ther22(5 Pt 1), 499–504 (1977).
  • Roos JC, Boer P, Koomans HA, Geyskes GG, Dorhout Mees EJ. Haemodynamic and hormonal changes during acute and chronic diuretic treatment in essential hypertension. Eur. J. Clin. Pharmacol.19(2), 107–112 (1981).
  • Roser M, Eibl N, Eisenhaber B et al. Gitelman syndrome. Hypertension53(6), 893–897 (2009).
  • Cruz DN, Simon DB, Nelson-Williams C et al. Mutations in the Na–Cl cotransporter reduce blood pressure in humans. Hypertension37(6), 1458–1464 (2001).
  • Ji W, Foo JN, O’Roak BJ et al. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat. Genet.40(5), 592–599 (2008).
  • Calo L, Ceolotto G, Milani M et al. Abnormalities of Gq-mediated cell signaling in Bartter and Gitelman syndromes. Kidney Int.60(3), 882–889 (2001).
  • Hebert SC, Mount DB, Gamba G. Molecular physiology of cation-coupled Cl- cotransport: the SLC12 family. Pflugers Arch.447(5), 580–593 (2004).
  • Maitland-van der Zee AH, Turner ST, Schwartz GL, Chapman AB, Klungel OH, Boerwinkle E. A multilocus approach to the antihypertensive pharmacogenetics of hydrochlorothiazide. Pharmacogenet. Genomics15(5), 287–293 (2005).
  • Turner ST, Schwartz GL, Chapman AB, Boerwinkle E. WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic. Hypertension46(4), 758–765 (2005).
  • Ellison DH, Loffing J. Thiazide effects and adverse effects. Insights from molecular genetics. Hypertension54(2), 196–202 (2009).
  • Moriguchi T, Urushiyama S, Hisamoto N et al. WNK1 regulates phosphorylation of cation–chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1. J. Biol. Chem.280(52), 42685–42693 (2005).
  • Wang Y, O’Connell JR, McArdle PF et al. From the cover: whole-genome association study identifies STK39 as a hypertension susceptibility gene. Proc. Natl Acad. Sci. USA106(1), 226–231 (2009).
  • Richardson C, Rafiqi FH, Karlsson HK et al. Activation of the thiazide-sensitive Na+–Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1. J. Cell Sci.121(Pt 5), 675–684 (2008).
  • Reungjui S, Pratipanawatr T, Johnson RJ, Nakagawa T. Do thiazides worsen metabolic syndrome and renal disease? The pivotal roles for hyperuricemia and hypokalemia. Curr. Opin. Nephrol. Hypertens.17(5), 470–476 (2008).
  • Savage PJ, Pressel SL, Curb JD et al. Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: the Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group. Arch. Intern. Med.158(7), 741–751 (1998).
  • ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA288(23), 2981–2997 (2002).
  • Lindholm LH, Persson M, Alaupovic P, Carlberg B, Svensson A, Samuelsson O. Metabolic outcome during 1 year in newly detected hypertensives: results of the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation (ALPINE study). J. Hypertens.21(8), 1563–1574 (2003).
  • Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet369(9557), 201–207 (2007).
  • Cooper-Dehoff RM, Wen S, Beitelshees AL et al. Impact of abdominal obesity on incidence of adverse metabolic effects associated with antihypertensive medications. Hypertension55(1), 61–68 (2009).
  • Pepine CJ, Handberg EM, Cooper-DeHoff RM et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil–Trandolapril Study (INVEST): a randomized controlled trial. JAMA290(21), 2805–2816 (2003).
  • Barzilay JI, Davis BR, Cutler JA et al. Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch. Intern. Med.166(20), 2191–2201 (2006).
  • Sica DA. Diuretic-related side effects: development and treatment. J. Clin. Hypertens. (Greenwich)6(9), 532–540 (2004).
  • Kasiske BL, Ma JZ, Kalil RS, Louis TA. Effects of antihypertensive therapy on serum lipids. Ann. Intern. Med.122(2), 133–141 (1995).
  • Lakshman MR, Reda DJ, Materson BJ, Cushman WC, Freis ED. Diuretics and β-blockers do not have adverse effects at 1 year on plasma lipid and lipoprotein profiles in men with hypertension. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Arch. Intern. Med.159(6), 551–558 (1999).
  • Williams K, Sniderman AD, Sattar N, D’Agostino R Jr, Wagenknecht LE, Haffner SM. Comparison of the associations of apolipoprotein B and low-density lipoprotein cholesterol with other cardiovascular risk factors in the Insulin Resistance Atherosclerosis Study (IRAS). Circulation108(19), 2312–2316 (2003).
  • Bia MJ, DeFronzo RA. Extrarenal potassium homeostasis. Am. J. Physiol.240(4), F257–F268 (1981).
  • DeFronzo RA, Felig P, Ferrannini E, Wahren J. Effect of graded doses of insulin on splanchnic and peripheral potassium metabolism in man. Am. J. Physiol.238(5), E421–E427 (1980).
  • Sterns RH, Feig PU, Pring M, Guzzo J, Singer I. Disposition of intravenous potassium in anuric man: a kinetic analysis. Kidney Int.15(6), 651–660 (1979).
  • DeFronzo RA, Sherwin RS, Dillingham M, Hendler R, Tamborlane WV, Felig P. Influence of basal insulin and glucagon secretion on potassium and sodium metabolism. Studies with somatostatin in normal dogs and in normal and diabetic human beings. J. Clin. Invest.61(2), 472–479 (1978).
  • Rowe JW, Tobin JD, Rosa RM, Andres R. Effect of experimental potassium deficiency on glucose and insulin metabolism. Metabolism29(6), 498–502 (1980).
  • Choi CS, Thompson CB, Leong PK, McDonough AA, Youn JH. Short-term K(+) deprivation provokes insulin resistance of cellular K(+) uptake revealed with the K(+) clamp. Am. J. Physiol. Renal Physiol.280(1), F95–F102 (2001).
  • Carter BL, Einhorn PT, Brands M et al. Thiazide-induced dysglycemia: call for research from a working group from the National Heart, Lung, and Blood Institute. Hypertension52(1), 30–36 (2008).
  • Knochel JP, Schlein EM. On the mechanism of rhabdomyolysis in potassium depletion. J. Clin. Invest.51(7), 1750–1758 (1972).
  • Agarwal R. Hypertension, hypokalemia, and thiazide-induced diabetes: a 3-way connection. Hypertension52(6), 1012–1013 (2008).
  • Pickkers P, Schachter M, Hughes AD, Feher MD, Sever PS. Thiazide-induced hyperglycaemia: a role for calcium-activated potassium channels? Diabetologia39(7), 861–864 (1996).
  • Sandstrom PE. Inhibition by hydrochlorothiazide of insulin release and calcium influx in mouse pancreatic β-cells. Br. J. Pharmacol.110(4), 1359–1362 (1993).
  • Zillich AJ, Garg J, Basu S, Bakris GL, Carter BL. Thiazide diuretics, potassium, and the development of diabetes: a quantitative review. Hypertension48(2), 219–224 (2006).
  • Shafi T, Appel LJ, Miller ER 3rd, Klag MJ, Parekh RS. Changes in serum potassium mediate thiazide-induced diabetes. Hypertension52(6), 1022–1029 (2008).
  • Smith SM, Anderson SD, Wen S et al. Lack of correlation between thiazide-induced hyperglycemia and hypokalemia: subgroup analysis of results from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. Pharmacotherapy29(10), 1157–1165 (2009).
  • Ayvaz G, Balos Törüner F, Karakoç A, Yetkin I, Cakir N, Arslan M. Acute and chronic effects of different concentrations of free fatty acids on the insulin secreting function of islets. Diabetes Metab.28(6 Pt 2), 3S7–3S12 (2002).
  • Eriksson JW, Jansson PA, Carlberg B et al. Hydrochlorothiazide, but not candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation: the Mechanisms For the Diabetes Preventing Effect of Candesartan (MEDICA) Study. Hypertension52(6), 1030–1037 (2008).
  • Reungjui S, Roncal CA, Mu W et al. Thiazide diuretics exacerbate fructose-induced metabolic syndrome. J. Am. Soc. Nephrol.18(10), 2724–2731 (2007).
  • Tikellis C, Cooper ME, Thomas MC. Role of the renin–angiotensin system in the endocrine pancreas: implications for the development of diabetes. Int. J. Biochem. Cell Biol.38(5–6), 737–751 (2006).
  • Tham DM, Martin-McNulty B, Wang YX et al. Angiotensin II is associated with activation of NF-κB-mediated genes and downregulation of PPARs. Physiol. Genomics11(1), 21–30 (2002).
  • Hadchouel J, Delaloy C, Faure S, Achard JM, Jeunemaitre X. Familial hyperkalemic hypertension. J. Am. Soc. Nephrol.17(1), 208–217 (2006).
  • Mayan H, Vered I, Mouallem M, Tzadok-Witkon M, Pauzner R, Farfel Z. Pseudohypoaldosteronism type II: marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density. J. Clin. Endocrinol. Metab.87(7), 3248–3254 (2002).
  • Maitland-van der Zee AH, Turner ST, Schwartz GL, Chapman AB, Klungel OH, Boerwinkle E. Demographic, environmental, and genetic predictors of metabolic side effects of hydrochlorothiazide treatment in hypertensive subjects. Am. J. Hypertens.18(8), 1077–1083 (2005).
  • Bozkurt O, de Boer A, Grobbee DE et al. Variation in renin–angiotensin system and salt-sensitivity genes and the risk of diabetes mellitus associated with the use of thiazide diuretics. Am. J. Hypertens.22(5), 545–551 (2009).
  • Carter BL, Ernst ME, Cohen JD. Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability. Hypertension43(1), 4–9 (2004).
  • Chanock SJ, Manolio T, Boehnke M et al. Replicating genotype–phenotype associations. Nature447(7145), 655–660 (2007).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.