Review Vascular effects of loop diuretics

Although it is generally believed that the beneficial effect of loop diuretics is the result of a rapid increase in diuresis, substantial evidence, from a large number of in vitro and in vivo experiments, has accumulated showing that administration of furosemide causes direct vascular effects, which probably contribute to its acute clinical effects, Several mechanisms are involved in the vascular response to loop diuretics. The role of the renin-angiotensin-aldosterone axis, prostaglandins and the direct vascular effects of loop diuretics on both the arterial and venous parts of the vasculature are discussed. Diuretic therapy has proved to be effective in the treatment of acute and chronic heart failure. The potent loop diuretics, furosemide and bumetanide, are frequently used in the treatment of disease states characterized by fluid and sodium retention. After intravenous administra­ tion of furosemide, clinical relief of symptoms often pre­ cedes the increase in diuresis in patients with acute heart failure, suggesting the presence of an extrarenal effect. Although it is generally believed that the beneficial effect of loop diuretics is the result of a rapid increase in diuresis, substantial evidence, from a large number of in vivo and in vitro experiments, has accumulated showing that adminis­ tration of furosemide causes vascular effects, which proba­ bly contribute to its acute clinical effects. At first sight the reports on the vascular non-diuretic effects of furosemide seem conflicting. However, a great deal of the disparity in the results seems to be due to differences in the vascular bed studied (arterial or venous, renal or pulmonary, etc.), the species studied, the timing (acute vs. chronic effects), systemic vs. local effects, direct vs, indirect effects and differences in disease states. In this paper the literature on vascular effects of loop diuretics t (with emphasis on furosemide) is reviewed with reference to the differences in experimental protocols. Finally, some general conclusions are drawn, and suggestions for future investigations are given.