Mechanism of Action
Loop diuretics act on the Na+-K+-2Cl- symporter (cotransporter) in the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption. This is achieved by competing for the Cl- binding site. Because magnesium and calcium reabsorption in the thick ascending limb is dependent on sodium and chloride concentrations (primarily on the recycling of the potassium due to the lack of the electropositive gradient generation), loop diuretics also inhibit their reabsorption. By disrupting the reabsorption of these ions, loop diuretics prevent the urine from becoming concentrated and disrupt the generation of a hypertonic renal medulla. Without such a concentrated medulla, water has less of an osmotic driving force to leave the collecting duct system, ultimately resulting in increased urine production. Loop diuretics cause an increase in the renal blood flow by this mechanism. This diuresis leaves less water to be reabsorbed into the blood, resulting in a decrease in blood volume.
The collective effects of decreased blood volume and vasodilation decrease blood pressure and ameliorate edema.
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