For this reason, there are more trials involving thiazide diuretics in the treatment of hypertension. There is also a theory that thiazide diuretics may have an additional mechanism of action involving direct vasodilation via relaxation of the vasculature. There is no literature to suggest that this mechanism of action may also be related to the loop diuretics. There is some in vitro evidence to support that hydrochlorothiazide causes vasodilation through the activation of potassium channels in the vasculature. Although difficult to determine in vivo, there is some support for this theory, but it was only achieved via IV infusion into a patient s forearm at doses higher than traditional oral therapeutic doses.
Some controversy surrounds the theory of thiazide vasodilation.
The question exists as to why thiazides are not effective in patients with poor renal function. If the mechanism of action involves direct vasodilation, thiazides should be effective in these patients, because vasodilation would not be affected by renal function. There are no factual conclusions regarding the direct vasodilatory effects of thiazides. Loop diuretics have never been included in the theory of direct vasodilation. The Pharmacological Basis of Therapeutics.