Chronic hyperinsulinemia enhances adrenergic vasoconstriction and decreases calcitonin gene-related peptide-containing nerve-mediated vasodilation in pithed rats.
The present study investigated the influence of chronic hyperinsulinemia on vascular responsiveness induced by adrenergic nerves and calcitonin gene-related peptide-containing (CGRPergic) nerves in pithed rats with insulin resistance. Male Wistar rats (6 weeks old) received 15% fructose solution in drinking fluid for 10 weeks (fructose-drinking rats: FDR), which resulted in significant increases in plasma levels of insulin, total cholesterol and triglyceride, and systolic blood pressure, as compared with control rats. Pithed FDR showed greater adrenergic nerve-mediated pressor response to spinal cord stimulation (SCS) at the lower thoracic vertebra (Th 9-12) and pressor response to exogenous noradrenaline than control rats. In pithed FDR with blood pressure artificially increased by continuous infusion of methoxamine and blockade of autonomic ganglia by hexamethonium, CGRPergic nerve-mediated depressor responses to SCS were significantly smaller than those in control rats, but depressor responses to other vasodilators such as acetylcholine, CGRP and sodium nitroprusside were similar to those in control rats. These results suggest that chronic hyperinsulinemia in FDR facilitates adrenergic nerve-mediated vasoconstriction, which is associated with attenuated CGRPergic nerve-mediated vasodilation.
Takatori
Shingo
S
Department of Clinical Pharmacy, School of Pharmacy, Shujitsu University, Okayama, Japan.
Zamami
Yoshito
Y
Mio
Mitsunobu
M
Kurosaki
Yuji
Y
Kawasaki
Hiromu
H
D000109:Acetylcholine / Q000494:pharmacology; D000320:Adrenergic Fibers / Q000737:chemistry* / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D006946:Hyperinsulinism / Q000150:complications / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000502:physiology; D014280:Triglycerides / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D002784:Cholesterol; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D009638:Norepinephrine