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AN ANALYSIS OF THE HAEMODYNAMIC EFFECTS OF TOLBUTAMIDE IN CONSCIOUS DOGS

1988; Wiley; Volume: 15; Issue: 5 Linguagem: Inglês

10.1111/j.1440-1681.1988.tb01091.x

1440-1681

King C. Lee, R Wilson, David C. Randall, Ralph J. Altiere, Judith A. Kiritsy‐Roy,

Nitric Oxide and Endothelin Effects

SUMMARY 1. In conscious chronically instrumented dogs, tolbutamide (5–45 mg/kg) induced significant dose‐related increases in mean arterial pressure and left ventricular enddiastolic pressure. 2. Cardiac output was descreased while heart rate, d(LVP)/dt, and regional myocardial performance at the left ventricle were not significantly affected. Computed total peripheral resistance was increased. 3. Pretreatment with the a‐antagonist phentolamine (1–1.5 mg/kg) abolished the pressor response. Furthermore, the pressor response to norepinephrine (0.1 μg/kg) was enhanced by pretreatment with tolbutamide (45 mg/kg). 4. In an isolated tissue preparation using ring segments of canine femoral arteries, neither tolbutamide nor its major hepatic metabolites (carboxytolbutamide, p ‐toluenesulfonamide and p ‐toluenesulfonylurea) caused any smooth muscle contraction. However, pretreatment of these tissues with 10– 4 , 10– 3 , or 10– 2 mol/l tolbutamide potentiated the contractile response to norepinephrine by up to 19% and to phenylephrine by up to 8%. 5. It was concluded that the pressor effect of tolbutamide arises by potentiating the a‐adrenoceptor mediated vasoconstrictor action of circulating endogenous catecholamines.