Comparative effects of calcium channel blockers and indomethacin on insulin secretion and blood pressure increase derived from alpha 1-adrenoceptor stimulation in the rabbit.
1. In conscious, fasted rabbits the intravenous infusion of the alpha 1-adrenoceptor agonist, amidephrine (3 and 10 micrograms kg-1 min-1) induced a dose related increase in insulin plasma levels. This effect was accompanied by a minor hypo- or hyperglycaemic response, depending on the dose of agonist infused. 2. A dose related increase in mean arterial pressure and reduction in heart rate were also found after amidephrine administration. 3. The insulin secretory response to amidephrine was not prevented in rabbits previously treated with atropine (5.26 micrograms kg-1 min-1). However, in the presence of muscarinic receptor blockade the bradycardic effect of amidephrine was either suppressed or attenuated. 4. Pretreatment with the calcium channel antagonist elgodipine (35 ng kg-1 min-1) or with indomethacin (0.66 mg kg-1 min-1) clearly blocked the effect of amidephrine on insulin secretion. 5. The haemodynamic changes induced by amidephrine were preserved in the presence of either verapamil (0.17 microgram kg-1 min-1) or indomethacin, whereas the hypertensive response was antagonized by elgodipine. 6. Our results suggest that the metabolic and haemodynamic changes mediated by amidephrine are two independent effects, insulin secretion requiring the presence of extracellular calcium and the synthesis of arachidonic acid metabolites.
García-Barrado
M J
MJ
Departamento de Farmacología, Facultad de Medicina, Universidad de Salamanca, Spain.
Reverte
M
M
Palomero
J
J
Moratinos
J
J
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011817:Rabbits
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D001786:Blood Glucose; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004983:Ethanolamines; D007328:Insulin; D018727:Muscarinic Antagonists; C063839:elgodipine; D001285:Atropine; C016980:amidephrine; D007213:Indomethacin