Altered Vascular Responsiveness: Initial Hypotensive Mechanism of Thiazide Diuretics

Abstract

Conclusion

In order to separate electrolyte and intravascular volume mechanisms of the thiazide diuretics from hemodynamic, local vascular, and neural factors mongrel dogs were studied before and 20 min after chlorothiazide (25 mg/kg, iv). Dose-response relationships of the mean arterial pressure curve following single bolus injections of norepinephrine and angiotensin were also obtained before and after chlorothiazide. Serum electrolytes, hematocrit, and plasma protein concentrations remained unchanged. Arterial pressure did not change, whereas cardiac output fell (p < .001). At each dose level the integrated pressure response to both pressor agents became significantly attenuated. These data indicate that the major immediate effect of the thiazide is local alteration in vascular responsiveness. Later, with natriuresis, electrolytic, volume, and possibly neural factors also participate.

The authors gratefully acknowledge the fine technical assistance of Mr. Alan Chang and Mrs. Janice Pfeffer and the secretarial work of Mrs. Irene Smith.