CARDIOVASCULAR EFFECTS OF ANTIHYPERTENSIVE DRUG DEBRISOQUIN - CONTRIBUTION TO PHARMACOLOGY OF CHRONIC TREATMENT .1. ONE-WEEK ADMINISTRATION TO DOGS

  • 1 January 1978
    • journal article
    • research article
    • Vol. 206  (1) , 123-131
Abstract
Debrisoquin (5 mg/kg per day) was administered to mongrel dogs on 7 consecutive days either i.v. or orally. At 16 h after the last dose, the animals were anesthetized with chloralose-urethane and subjected to several hemodynamic and biochemical measurements which serve for a comparison with the later results or chronic treatment. Aortic blood pressure, cardiac output, heart rate (after vagotomy) and pressor responses to bilateral carotid occlusion were decreased by debrisoquin; cardiac contractility and left ventricular end-diastolic pressure remained unaffected. The fall in vascular resistance of the perfused hind legs which occurred after cutting the lumbar sympathetic chain was smaller after debrisoquin than in controls. Increases in perfusion pressure elicited in the hind legs by electrical stimulation of the peripheral end of the sectioned lumbar sympathetic chain or by i.a. (intraarterial) injection of tyramine were inhibited by treatment with debrisoquin. The vascular responses to i.a. injections of norepinephrine, angiotensin and acetylcholine remained unchanged. Isolated perfused mesenteric artery preparations obtained from dogs pretreated with debrisoquin showed reduced pressor responses to periarterial nerve stimulation. Dose-response curves for the pressor effect of norepinephrine were not altered by debrisoquin. Debrisoquin administered i.v. or orally depleted to a similar extent the stores of norepinephrine in the heart, spleen, mesenteric and femoral arteries.

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