EFFECT OF CHLORTHALIDONE ON BLOOD VESSELS

¹ Department of Pharmacology, University of Toronto, Toronto, Canada

In previous experiments we found that prolonged treatment with hydrochlorothiazide depresses norepinephrine vasoconistriction. In the present study the effect of chlorthalidone was investigated. In vitro, norepinephrine produced significantly less contraction in the mesemiteric veins of rabbits treated with chlorthalidone (30 mg/day) for 6 to 10 weeks than in the veins of control animals. In the same vessels the effects of acetylcholine, barium chloride, angiotensin, papaverine and adenosine triphosphate were not altered significantly. One other group of rabbits was treated with 1, 3, 7.5 or 15 mg/day of chlorthalidone for 6 to 10 weeks and the magnitude of the depression of the norepinephrine effect was related to the dose of chlorthalidone. In dogs after 8 to 10 weeks of treatment with chlorthalidone (50 mg/day), the pressure increment in the resistance vessels produced by i.a. norepinephrine or by stimulation of lumbar sympathetic nerves was substantially less in treated than in control animals. The effects of i.a. angiotensin and adenosine triphosphate, however, were similar in treated and control dogs. Chlorthalidone treatment in dogs increased calcium and decreased potassium in plasma (P < .01). Sodium or potassium content of the iliac artery and vein of chlorthalidone-treated rabbits and dogs was not consistently altered. It is proposed that diminished response to norepinephrine may be a factor responsible for the antihypertensive effect encountered after prolonged administration of chlorthalidone or hydrochlorothiazide.

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