title: Acute hyperglycemia and hyperinsulinemia enhance adrenergic vasoconstriction and decrease calcitonin gene-related peptide-containing nerve-mediated vasodilation in pithed rats.
abstract: Recent clinical studies have demonstrated that transient postprandial hyperglycemia and hyperinsulinemia may contribute to the development of hypertension. Therefore, we investigated the influence of acute hyperglycemia and/or hyperinsulinemia induced by glucose or insulin infusion on neuronal and humoral control of vascular tone in rats. Euglycemic male Wistar rats were pithed under anesthesia and arterial blood pressure was measured. Changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin II, calcitonin gene-related peptide (CGRP), acetylcholine and sodium nitroprusside (SNP) were studied by infusing various concentrations of glucose or insulin. Continuous glucose infusion, which increased both blood glucose and serum insulin levels, significantly augmented adrenergic nerve-mediated pressor responses to SCS without affecting pressor responses to injection of noradrenaline or angiotensin II. In pithed rats with artificially increased blood pressure and blockade of autonomic outflow, glucose infusion attenuated CGRPergic nerve-depressor responses to SCS without affecting depressor responses to injection of CGRP, acetylcholine or SNP. In pithed rats treated with octreotide, which increased blood glucose without increasing serum insulin levels, glucose infusion caused only significant augmentation of adrenergic nerve-mediated pressor responses. Combined infusion of insulin and glucose, which resulted in increased serum insulin levels with euglycemia, significantly augmented adrenergic nerve-mediated pressor responses and attenuated CGRPergic nerve-mediated depressor responses. The present results suggest that acute hyperglycemia and hyperinsulinemia increase adrenergic nerve-mediated vasoconstriction, which in turn blunts CGRPergic nerve function, and that the increase in plasma insulin concentration associated with hyperglycemia may be responsible for the alteration of neuronal vascular regulation.
authors: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors: Yoshito
authors: Y
authors: Zamami
authors: Shingo
authors: S
authors: Takatori
authors: Kousuke
authors: K
authors: Yamawaki
authors: Satoko
authors: S
authors: Miyashita
authors: Mitsunobu
authors: M
authors: Mio
authors: Yoshihisa
authors: Y
authors: Kitamura
authors: Hiromu
authors: H
authors: Kawasaki
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000208:Acute Disease; D000320:Adrenergic Fibers / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000503:physiopathology*; D006946:Hyperinsulinism / Q000503:physiopathology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D015282:Octreotide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D005947:Glucose; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D015282:Octreotide; D009638:Norepinephrine