The place of diuretics in the treatment of hypertension: a historical review of classical experience over 30 years.

Thiazide diuretics have been the mainstay of antihypertensive therapy for over 30 years. Their precise mechanism of antihypertensive action is still incompletely understood. They reduce arterial pressure initially through a fall in plasma volume and cardiac output. However, with chronic administration cardiac output tends to return toward pretreatment levels, suggesting that the long-term pressure reduction is mediated through a reduction in vascular resistance. Although multiple lines of evidence suggest that salt and water loss is an essential part of the mechanism, at least in some cases an indirect vasodilator effect may play a role as well. The antihypertensive efficacy of diuretics is proven; they are at least as effective as other classes of antihypertensive drugs. They have been shown to protect against stroke, but not against mortality from myocardial infarction. There is some concern about the metabolic side effects, such as hypokalemia, hyperglycemia, and hyperlipidemia. In order to minimize these side effects the lowest effective dose should be used. Diuretics are likely to remain first-line antihypertensive agents, but they should be considered as one of several possible choices for the initial therapy among other classes, such as beta-blockers, ACE inhibitors, or calcium entry blockers.