What physiologic effect do thiazide diuretics specifically target to lower blood pressure?

Thiazide diuretics primarily work by decreasing sodium retention in the kidneys. They act on the distal convoluted tubule, where they inhibit the sodium-chloride co-transporter. By preventing the reabsorption of sodium, these diuretics promote the excretion of sodium (and consequently water), leading to a reduction in blood volume. This decrease in blood volume is significant because it effectively lowers cardiac output and, as a result, blood pressure.

Moreover, the reduction in sodium levels not only contributes to decreased fluid retention but also affects vascular resistance. Lower sodium levels can lead to relaxation of vascular smooth muscle and further decreased blood pressure. Thus, the mechanism of action of thiazide diuretics in targeting sodium levels is a primary reason for their efficacy in treating hypertension.