An analysis of the haemodynamic effects of tolbutamide in conscious dogs.
1. In conscious chronically instrumented dogs, tolbutamide (5-45 mg/kg) induced significant dose-related increases in mean arterial pressure and left ventricular end-diastolic pressure. 2. Cardiac output was decreased 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 alpha-antagonist phentolamine (1-1.5 mg/kg) abolished the pressor response. Furthermore, the pressor response to norepinephrine (0.1 microgram/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-toluene-sulfonamide and p-toluene-sulfonylurea) 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 alpha-adrenoceptor mediated vasoconstrictor action of circulating endogenous catecholamines.
Lee
K C
KC
Department of Physiology and Biophysics, Albert B. Chandler Medical Center, University of Kentucky, Lexington.
Wilson
R A
RA
Randall
D C
DC
Altiere
R J
RJ
Kiritsy-Roy
J A
JA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D014044:Tolbutamide / Q000097:blood / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D014044:Tolbutamide; D003000:Clonidine; D009638:Norepinephrine; D010646:Phentolamine