title: Mechanisms mediating insulin-induced hypotension in rats. A role for nitric oxide and autonomic mediators.
abstract: The mechanisms associated with insulin-induced cardiovascular inhibitory responses were evaluated in untreated normal rats and in normal rats pretreated with an antagonist of nitric oxide (NO) production (L-NAME), with cholinergic, alpha- and beta-adrenergic antagonists, or after ganglionic blockade. Male Wistar rats were anesthetized with a mixture of urethane and alpha-chloralose and placed on a electric heating pad. The femoral artery and vein were cannulated for measurements of mean arterial pressure (MAP), heart rate, plasma glucose, blood sampling, and intravenous injections. Intravenous injection of insulin (5.0 U/kg) in untreated rats resulted in a significant and sustained decrease in arterial blood pressure (average 24%) and in a slight decrease in heart rate. These cardiovascular responses were blocked by L-NAME and by the cholinergic antagonist atropine, suggesting an involvement of NO and the cholinergic receptors, or an effect of insulin on the central nervous system parasympathetic center. The ganglionic blocker hexamethonium attenuated the insulin-induced response. On the other hand, the hypotensive effect of insulin persisted after sympathetic blockade with the alpha-1 antagonist prazosin and the beta-1 antagonist atenolol. We conclude that the insulin-induced decrease in blood pressure is due to both increased cholinergic outflow and to NO production and that an enhanced sympathetic activity possibly mediated by a reactive release of norepinephrine or epinephrine modulates this response.
authors.affiliation: Department of Physiology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Dunbar
authors.forename: D S
authors.initials: DS
authors.lastname: O'Leary
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Wright-Richey
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015331:Cohort Studies; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D018738:Hexamethonium / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009569:Nitric Oxide; D018738:Hexamethonium; D001262:Atenolol; D001285:Atropine; D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin