How diuretics lower blood pressure.

Thiazides produce an average loss of 2 L of extracellular fluid volume, of which about 300 ml is plasma volume, during the first 48 hours of administration, and this reduction is maintained without further loss for as long as the drug is given. Do thiazides lower blood pressure by volume depletion or by direct vasodilator action? As evidence against the vasodilator theory, these facts may be adduced: (1) thiazides do not lower blood pressure in patients (with renal disease) who cannot obtain a diuresis, and (2) other diuretics and diets very low in sodium also reduce blood pressure and volume to a similar degree. A related hypothesis is that thiazides reduce total peripheral vascular resistance (TPR) by "dehydrating" vascular walls. However, direct measurements in small arteries failed to confirm such changes. There is, however, a fall in TPR after long-term treatment, although initially cardiac output falls and TPR remains unchanged. How these long-term readjustments occur remains unknown, although several hypotheses have been advanced.