Key result
Thiazide diuretic chronic reduction of arterial pressure is dependent upon decreased plasma volume as a trigger and is sustained by direct inhibition of vasoconstriction.
Why the study?
Despite over five decades of research, the extrarenal target mediating thiazide diuretic-induced vascular dilation and arterial pressure reduction remains unidentified, and comprehensive reviews evaluating these mechanisms are lacking.
This review highlights the lack of consensus on the extrarenal target of thiazide diuretics for chronic arterial pressure reduction and proposes a working model for future investigations.
Thiazide diuretics may lower pressure via volume trigger plus vasoconstriction inhibition; leaves open extrarenal targets for validation.
Thiazide diuretic (TZD)-mediated chronic reduction of arterial pressure is thought to occur through decreased total peripheral vascular resistance. Further, the decreased peripheral vascular resistance is accomplished through TZD activation of an extrarenal target, resulting in inhibition of vascular constriction. However, despite greater than five decades of investigation, little progress has been made into the identification of the TZD extrarenal target. Proposed mechanisms range from direct inhibition of constrictor and activation of relaxant signaling pathways in the vascular smooth muscle to indirect inhibition through decreased neurogenic and hormonal regulatory pathways. Surprisingly, particularly in view of this lack of progress, comprehensive reviews of the subject are absent. Moreover, even though it is well recognized that 1) several types of hypertension are insensitive to TZD reduction of arterial pressure and, further, TZD fail to reduce arterial pressure in normotensive subjects and animals, and 2) different mechanisms underlie acute and chronic TZD, findings derived from these models and parameters remain largely undifferentiated. This review 1) comprehensively describes findings associated with TZD reduction of arterial pressure; 2) differentiates between observations in TZD-sensitive and TZD-insensitive hypertension, normotensive subjects/animals, and acute and chronic effects of TZD; 3) critically evaluates proposed TZD extrarenal targets; 4) proposes guiding parameters for relevant investigations into extrarenal TZD target identification; and 5) proposes a working model for TZD chronic reduction of arterial pressure through vascular dilation.
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Rapoport et al. (2019) conducted a review in Hypertension. Thiazide diuretics was evaluated. Thiazide diuretic chronic reduction of arterial pressure is dependent upon decreased plasma volume as a trigger and is sustained by direct inhibition of vasoconstriction.
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