Mechanism of antihypertensive effect of thiazide diuretics

Shah, Shaukat; Khatri, Ibrahim M.; Freis, Edward D.

doi:10.1016/0002-8703(78)90303-4

Cited by 123 publications

(58 citation statements)

References 28 publications

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“…The effects of diuretic therapy on circula tory parameters have been well described [1,2]. Following their acute administration, thia zide agents reduce extracellular fluid volume and reduce venous return; in accord with the Frank-Starling mechanism the cardiac output is lowered and systemic vascular resistance is increased.…”

Section: Cascade Of Events Following Early Diuretic Therapy Of Heart mentioning

confidence: 99%

Haemodynamic Impact of Diuretic Therapy in Chronic Heart Failure

Silke

1994

Cardiology

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An immediate improvement in haemodynamic variables and cardiac performance is achieved in chronic heart failure following diuretic therapy, primarily due to reductions in plasma and extracellular fluid volumes. Humoral markers of these alterations are increased plasma renin, angiotensin and aldosterone levels; these increase maximally over the ñrst week of treatment but attenuate during sustained therapy. There are reciprocal alterations in plasma α-atrial natriuretic peptide levels. These findings suggest that the initial volume contraction is maintained, though somewhat attenuated, during chronic therapy. The neurohumoral consequences of diuretic therapy are of particular interest in heart failure, as they may contribute to diuretic resistance. Activation of the renin-angiotensin system favours the proximal tubular reabsorption of sodium and water, which may result in dilutional hyponatraemia. Diuretics have both direct vascular and non-vascular (volume-dependent) haemodynamic actions. Together these substantially reduce the left heart filling pressure (-29%) with a consequent fall in cardiac output ( 10%). Systemic vascular resistance initially increases but subsequently normalizes, allowing cardiac output to return towards control values. Haemodynamic tolerance to diuretics does not usually occur during sustained oral therapy; additionally, echocardiographic contractility indices and exercise capacity may increase. The vasodilator activity of the diuretics is due to prostaglandin release; the initial pressor action is due to activation of the renin-angiotensin system. Direct pulmonary vasodilatation with improved pulmonary compliance remains an interesting possibility. Over the longer term, substantial reductions in left heart filling pressure during exercise occur at unaltered cardiac output. The impact of diuretic therapy on the underlying myocardial disease process is unknown. There is little direct evidence of ventricular remodelling or of improved intrinsic cardiac performance (as distinct from that due to altered loading conditions). In the absence of such information, it would appear reasonable to combine diuretic therapy with a vasodilator or angiotensin converting enzyme inhibitor, even in patients symptomatically well controlled on diuretic alone.

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Section: Cascade Of Events Following Early Diuretic Therapy Of Heart mentioning

confidence: 99%

Haemodynamic Impact of Diuretic Therapy in Chronic Heart Failure

Silke

1994

Cardiology

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“…Thus, for example in chronic antihypertensive mangement, attenuation of the increase in plasma urate induced by hydrochlorothiazide has been reported when the patients have been treated with a combination of this drug with captopril (Weinberger, 1982 *P < 0.05, **P < 0.01, n = number of subjects peripheral resistance (Shah et al, 1978). The more sustained shrinkage of plasma volume that occurs with the longer-acting members of the thiazide group of diuretics explains the greater effectiveness of these compounds as antihypertensive agents when compared to loop diuretics such as frusemide (Anderson et al, 1971).…”

Section: Intrarenal Effectsmentioning

confidence: 99%

Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions‐parallels and contrasts.

Lant

1987

Brit J Clinical Pharma

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1 The emergence of diuretic drugs and angiotensin converting enzyme (ACE) inhibitors ranks amongst the major therapeutic advances of modern medicine. The discovery of these drug groups arose largely by chance, yet each has dramatically influenced the treatment of congestive cardiac failure and arterial hypertension. 2 The central role which diuretics have had in the management of both oedema and hypertension hinges on their ability to induce a net renal excretion of solute and water by selective interference with either active or passive ion transport processes in different segments of the nephron. Irrespective of sites of action, the continued antihypertensive action of diuretics is characterized by a reduction in plasma volume and extracellular fluid (ECF) volume that lasts for as long as the diuretic is given. The mechanism of this effect remains unclear but may involve autoregulatory reactions that leave cardiac output unaltered but maintain a sustained reduction in total peripheral resistance. 3 ACE inhibitors also lower blood pressure by decreasing total peripheral resistance, leaving cardiac output, plasma volume and ECF volume unchanged. The detailed way these haemodynamic changes are achieved remains unknown but inhibition of converting enzyme present not only in the kidney but also in many extrarenal tissue sites, appears important. In both hypertension and cardiac failure, however, the kidney acts as a key target organ for ACE inhibitors. The increased renal vascular resistance and inappropriate renal salt excretion are reversed with enhanced renal blood flow and saluresis. Both angiotensin II (All) and vasopressin-mediated contraction of glomerular mesangial cells is inhibited, making glomerular filtration more efficient. Reduced aldosterone secondary to blockade of AII formation contributes to saluresis whilst encouraging positive potassium balance. ACE inhibition also impairs breakdown of kinins which may contribute to intrarenal and peripheral vasodilation either on their own or via release of prostaglandins and other vasoactive substances.4 The hypotensive actions of diuretics are potentiated by ACE inhibition primarily through blockade of AII formation and prevention of secondary aldosteronism. In combination, these drugs permit low doses to be used because of their synergistic effects. 5 Caution has to be exercised whenever ACE inhibition is used, without and especially with diuretics, in the management of renovascular hypertension and other low-perfusion states. In these circumstances, AII plays an important autoregulatory role in preserving glomerular filtration through an increase in post-glomerular resistance. Suppression of angiotensin formation with an ACE inhibitor can cause a critical reduction in glomerular perfusion. On the other hand, with careful titration, the dual actions of low-dose loop diuretics and an ACE inhibitor may be highly efficacious in treating severe heart failure and totally prevent such serious metabolic sequelae as azotaemia and hyponatraemia. 6 Unlike the experien...

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“…However, the long-term reductions in BP that occur with thiazides are likely manifested through other mechanisms, e.g. non-diuretic actions within the kidney [19,20]. The data presented within this study, as well as other recently published studies, add clinical credence to this mechanistic argument [12].…”

Section: Discussionmentioning

confidence: 56%

Are Thiazide Diuretics Safe and Effective Antihypertensive Therapy in Kidney Transplant Recipients?

Taber

Srinivas²,

Pilch

et al. 2013

Am J Nephrol

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Background/Aims: There are no published studies assessing the safety and efficacy of thiazides as antihypertensives in kidney transplantation (KTX). Methods: This was a longitudinal retrospective cohort study conducted in adult KTX recipients. Patients were grouped based on receiving thiazides following KTX. Safety and efficacy comparisons were made between thiazide recipients and unexposed patients, as well as change in blood pressure (BP) within thiazide patients. Results: 1,093 patients were included (thiazide group: 108, unexposed group: 985). Mean follow-up was 7.3 ± 4.5 years. Thiazide recipients were older (53 ± 11 vs. 48 ± 13 years, p < 0.001) and more likely to be female (52 vs. 41%, p = 0.023) and have pre-KTX hypertension (97 vs. 88%, p = 0.004) or diabetes (36 vs. 27%, p = 0.035). After controlling for baseline differences, safety analysis revealed thiazide recipients were not more likely to be readmitted to the hospital, but were at higher risk to develop hyperkalemia (56 vs. 38%, p < 0.001) or hypokalemia (28 vs. 18%, p = 0.010), with similar rates of hypotension, decreased estimated glomerular filtration rate, graft loss and death. Efficacy analysis demonstrated systolic (147 ± 17 to 139 ± 18 mm Hg, p < 0.001) and diastolic (79 ± 9 to 77 ± 11 mm Hg, p < 0.001) BPs were significantly reduced after thiazide initiation. Compared to unexposed patients, thiazide recipients had higher mean BPs during the entire follow-up (142/78 vs. 136/77, p < 0.001), with similar BPs while on thiazides and comparable rates of goal BPs (<130/80 mm Hg, 32 vs. 36%, p = 0.219). Conclusions: In KTX, based on long-term outcomes, thiazides appear to be safe and effective antihypertensives; in the short-term, thiazides may increase the risk of developing potassium disturbances.

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Mechanism of antihypertensive effect of thiazide diuretics

Cited by 123 publications

References 28 publications

Haemodynamic Impact of Diuretic Therapy in Chronic Heart Failure

Haemodynamic Impact of Diuretic Therapy in Chronic Heart Failure

Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions‐parallels and contrasts.

Are Thiazide Diuretics Safe and Effective Antihypertensive Therapy in Kidney Transplant Recipients?

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