Hypotensive Action of Hydrochlorothiazide and Clorexolone in the Conscious Normotensive Dog

Abstract

DIURETIC drugs of the benzothiadiazide type such as chlorothiazide and hydrochlorothiazide will cause a fall in both systolic and diastolic blood pressure in some cases of hypertension^1–4. The mechanism by which these diuretic agents produce a fall in blood pressure has not, however, been elucidated. Tapia, Dustan, Schneckloth, Corcoran and Page⁵ and Dustan, Cumming, Corcoran and Page⁶ have suggested that this hypotensive activity is due to potassium depletion and a reduction of blood volume. In contrast, Hollander, Chabanian and Wilkins⁷ state that there must be an additional mechanism as well as the effects on electrolyte balance. Possibly one of the reasons why the mechanism of hypotensive activity of these drugs has not been elucidated is that they do not cause a fall in arterial pressure in the anæsthetized animal^8–10. For example, no hypotensive effect was produced by hydrochlorothiazide in the normal dog under pentobarbitone⁸ or in the neurogenic hypertensive dog under chloralose anæsthesia¹⁰. We feel, therefore, that it may be of interest to report that both hydrochlorothiazide and a new non-benzothiazide diuretic clorexolone^11,12 produce a reduction of arterial pressure of the conscious normotensive dog.