Mechanism of Antihypertensive Action of Prolonged Administration of Hydrochlorothiazide in Rabbit and Dog

Abstract

The effect of hydrochlorothiazide on vascular reactivity to various drugs was studied in rabbit and dog. In rabbit, dose response in the mesenteric artery and vein was examined in vitro following a treatment with hydrochlorothiazide for 6 to 10 weeks. Norepinephrine produced significantly less contraction in the vein of treated than of control animals (P < 0.005), but the effect of aeetylcholine, barium chloride, angiotensin, papaverine, and adenosine triphosphate (ATP) was not altered. In the hindlimb of dogs treated with hydrochlorothiazide for 6 to 8 weeks, intra-arterial norepinephrine caused substantially less pressure increment in the resistance vessels, perfused at constant flow rate, of treated than of control animals. Stimulation of lumbar sympathetic nerves also augmented pressure in the femoral artery less in treated than in control dogs. No such difference in the effect of intra-arterial ATP or angiotensin was observed between the two groups of animals. Preliminary results both in the rabbit and in the dog failed to demonstrate a significant alteration in water, sodium, potassium, and calcium content of the iliap artery or vein after hydrochlorothiazide treatment. Diminished response to norepinephrine in the vessels after hydrochlorothiazide treatment may be responsible for the antihypertensive effect after the prolonged administration of this drug.

Torasemide Inhibits Angiotensin II–Induced Vasoconstriction and Intracellular Calcium Increase in the Aorta of Spontaneously Hypertensive Rats

“…4 Animal experiments have shown that diuretics reduce the vascular responsiveness to vasoconstrictor agonists like norepinephrine and angiotensin II (Ang II). 5,6 In addition, in hypertensive patients it was shown that long-term use of diuretics desensitizes the vasculature in its response to endogenous vasoconstrictor hormones. 7 Torasemide is a pyridil sulfonil urea class compound whose chemical structure places it between loop diuretics and Cl Ϫ channel blockers.…”

Cardiac cellular actions of hydrochlorothiazide

“…It is known, however, that in the long term, thiazide diuretics appear to reduce blood pressure by reducing peripheral resistance rather than by their diuretic effects [4], suggesting a direct vascular dilating action. This action was also demonstrated in rabbits and dogs [5].…”

Investigations on the Antihypertensive Activity of Timolol and Bendroflumethiazide and the Combination in Dogs and Rats

“…1971). On the other hand, it is well known that the thiazideinduced saluresis is accompanied by a reduction in plasma volume and a decrease in cardiac output (WILSON & -IS 1959;DUSTAN et al 1974). Furthermore, in a study of timolol in hypertensive patients, there was no correlation between the hypotensive efficacy of timolol and basal plasma renin activity values, or in their furosemide-induced increase ( LYDTIN et al 1974).…”