Why Do Thiazide Diuretics Lower Blood Pressure in Essential Hypertension?

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Abstract
The action of thiazides in lowering arterial pressure is still mysterious. Their diuretic action tends to produce a slightly lowered blood volume. This would by itself tend to reduce cardiac output and arterial pressure. Moreover, it would also potentiate the action of any other drugs such as ganglionic blockers or guanethidine, which increase the volume of the veins and venules. More importantly, thiazides also tend to decrease body sodium and extracellular fluid volume. This tendency to Na depletion brings about adaptive responses in the kidney, so that the body Na content is diminished only a little. Yet this tendency to Na depletion and the adaptation to it somehow oppose the fundamental hypertensive diathesis in essential hypertension and produce a widening of systemic arterioles and a decrease in peripheral resistance. Some of the decrease in resistance may be related to a diminished effect of the sympathetic nervous system. At any rate, the tendency to Na depletion may be involved in the antihypertensive action, since the eating of really large quantities of salt can abolish the antihypertensive effect of the thiazides.