Comparison of the effects of endothelin and Bay k 8644 on cardiohemodynamics in anesthetized pigs.
The effects of endothelin on cardiohemodynamics in anesthetized open-chest pigs were compared with those of the Ca2+ channel agonist Bay k 8644. I.v. administration of endothelin (0.1-1 microgram/kg) dose relatedly decreased coronary blood flow velocity (CFV), cardiac output, the maximal rate of rise in left ventricular pressure (LV dP/dtmax) and heart rate, and increased systolic and diastolic blood pressure and systemic vascular resistance. Bay k 8644 (0.1-30 micrograms/kg) showed similar effects on cardiohemodynamics, except that it caused a substantial increase in LV dP/dtmax and did not change stroke volume. I.c. administration of endothelin (0.1-1 microgram) into the left circumflex coronary artery (LCX) produced a dose-dependent and sustained decrease in CFV followed by a marked increase in the ST segment of epicardial electrocardiograms and a depression in myocardial shortening in the region supplied by LCX. An increase in left ventricular end-diastolic pressure and a reduction in LV dP/dtmax were also observed after endothelin. In contrast, Bay k 8644 caused a transient decrease in CFV and an increase in LV dP/dtmax, without causing any changes indicative of myocardial ischemia. Although the reduction in CFV after i.c. endothelin was not affected by i.v. infusion of nicardipine (1 microgram/kg per min), the reduction in CFV observed after i.c. Bay k 8644 was significantly suppressed (P less than 0.05). We conclude that endothelin is a more potent coronary vasoconstrictor than Bay k 8644 and provokes marked myocardial ischemia.
Adachi
H
H
Department of Pharmacology, Eisai Tsukuba Research Laboratories, Ibaraki, Japan.
Shoji
T
T
Goto
K
K
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D016232:Endothelins / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D009200:Myocardial Contraction / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D016232:Endothelins; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester