Circulatory Responses to Norepinephrine After Prolonged Treatment with Chlorothiazide

Cardiovascular responses to graded intravenous infusions of norepinephrine were measured in untreated control dogs and in dogs treated for five weeks with oral chlorothiazide. Observations were made both before and after administration of a ganglionic blocking agent. In these experiments, chlorothiazide reduced the responses of the peripheral blood vessels to the vasoconstrictor effect of norepinephrine. This effect was apparent both before and after ganglionic blockade, suggesting that modification of resting neurogenic vasomotor tone did not play a major role in the reduced responsiveness. Cardiac output and heart rate were greater during norepinephrine infusion in treated dogs before hexamethonium. Output and rate became similar in both treated and untreated groups after hexamethonium. The results provide additional evidence to support the hypothesis that chlorothiazide reduces the effectiveness of cardioinhibitory reflexes.