Glucagon pharmacodynamics and modulation of sympathetic nerve and norepinephrine-induced constrictor responses in the superior mesenteric artery of the cat.
The aim of this study was to assess whether the pancreatic peptide glucagon was capable of inhibiting nerve- and norepinephrine-induced vasoconstrictor responses in the superior mesenteric artery of the anesthetized cat. Intra-arterial dose-response curves for glucagon and norepinephrine were analyzed by nonlinear regression to estimate the maximal response (maximal dilation, 163%; maximal constriction, 110%) in terms of percent change in superior mesenteric artery conductance and dose of glucagon or norepinephrine required to produce 50% of the maximal response (0.98 and 0.38 micrograms/kg/min, respectively). Constrictor responses (3-min duration) were only weakly inhibited by glucagon. Peak constrictor responses induced by low-dose i.a. infusions of norepinephrine were significantly inhibited (39%) by the high dose of glucagon, whereas the high-dose norepinephrine peak constrictor responses were unaffected by any dose of glucagon. Intermediate and high doses of glucagon significantly inhibited the low-frequency (2 Hz) nerve-induced peak constrictions (19% and 34%, respectively). The higher frequency (6 Hz) nerve-induced peak constrictor responses were not significantly affected by glucagon. Vascular escape from nerve- and norepinephrine-induced peak constrictor responses was not related to the degree of initial constriction nor were they affected by glucagon. Glucagon levels produced by our i.a. infusions were estimated to be well outside the pathophysiological range. We conclude that glucagon is not an effective inhibitor of constrictor responses in the superior mesenteric artery and is unlikely to have such an effect at physiological levels.
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
M S
MS
D'Almeida
W W
WW
Lautt
D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005934:Glucagon / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D005934:Glucagon; D009638:Norepinephrine