Sympathetic activation by chronic insulin treatment in conscious rats.
Normal male Wistar rats pretreated with insulin for 12 days were studied to determine if chronic insulin treatment would reproduce the cardiovascular changes occurring in obese rats with hyperinsulinemia. After 12 days, plasma insulin rose while plasma glucose fell, but basal pressures recorded while the rats were awake remained unchanged. Depressor and tachycardic responses to isoproterenol were enhanced, thereby suggesting that beta adrenergic responsiveness had been increased. By contrast, cardiovascular responses to angiotensin were unaltered. The same rats were then anesthetized with urethane-chloralose, and reflex responses, elicited by elevating blood pressure with phenylephrine or lowering it with sodium nitroprusside, were compared with those from control rats that had not been treated with insulin. Reflex inhibition of splanchnic nerve activity during phenylephrine infusion was weaker, whereas reflex tachycardia during nitroprusside infusion was stronger in insulin-treated rats. However, cardiovascular and sympathetic responses elicited by electrical stimulation of the posterior hypothalamus were the same whether the rats had been treated with insulin or not. Although these differences imply that hyperinsulinemia cannot be solely responsible for the cardiovascular dysfunction in obesity, our results nonetheless suggest that by increasing beta adrenergic responsiveness and reducing sympathetic inhibition, excess insulin can cause sympathetic predominance even without elevating blood pressure.
Department of Pharmacology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City.
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Buñag
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Krizsan-Agbas
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Itoh
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004347:Drug Interactions; D004558:Electric Stimulation; D007031:Hypothalamus / Q000187:drug effects; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects*
D001786:Blood Glucose; D007328:Insulin; D000804:Angiotensin II; D010656:Phenylephrine; D007545:Isoproterenol