The inhibition by glucagon of the vasoconstrictor actions of noradrenaline, angiotensin and vasopressin on the hepatic arterial vascular bed of the dog.
1 The hepatic artery of the anaesthetized dog was cannulated and perfused from a femoral artery, the blood flow and perfusion pressure being monitored continuously. The sympathetic periarterial nerves were divided. 2 Dose-dependent increases in hepatic arterial vascular resistance (HAVR) resulted from intra-arterial injections of noradrenaline, angiotensin and vasopressin. 3 Single injections of glucagon (100 mug, i.a.) caused a transient significant fall in HAVR of 19.9 +/- 3.2%, and infusions of 25 mug/min of glucagon intra-arterially caused maintained reductions in HAVR of 16.9 +/- 4.2%. 4 After single injections of 100 mug glucagon intra-arterially the vasoconstrictor responses to noradrenaline, angiotensin, and vasopressin were reduced by about 85-95%. Recovery occurred in 8-10 minutes. 5 Intra-arterial infusions of glucagon, 2.5-50.0 mug/min, reduced the effects of test doses of noradrenaline, angiotensin and vasopressin throughout the period of the infusions. 6 Dose-response curves to the constrictor agents were constructed before, during and after intra-arterial infusions of 25 mug/min of glucagon. Glucagon caused a parallel shift of the curves for noradrenaline and angiotensin to the right, with no suppression of the maximum response. 7 Infusions of glucagon shifted the dose-response curve for vasopressin to the right, but, in contrast to noradrenaline and angiotensin, the shift was nonparallel and there was a suppression of the maximum response by about one-half. 8 A large dose of insulin, 10 iu, transiently reduced HAVR and caused a weak and very transient inhibition of the effect of test doses of noradrenaline. The characteristics of these effects were quite different from those of glucagon. 9 It is possible that the antagonism by glucagon of the vasoconstrictor responses of the hepatic arterial vasculature may be important in protecting this vascular bed from the effects of concomitantly released vasoconstrictor agents.
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005934:Glucagon / Q000494:pharmacology*; D008102:Liver Circulation / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents; D014667:Vasopressins / Q000037:antagonists & inhibitors*
D014662:Vasoconstrictor Agents; D014667:Vasopressins; D000804:Angiotensin II; D005934:Glucagon; D009638:Norepinephrine