Effects of insulin on vascular responses to spinal cord stimulation and vasoactive agents in pithed rats.
1. Effects of insulin (2-600 pmol kg(-1) min(-1), i.v.) on vascular responses to spinal cord (lower thoracic vertebra, Th 9-12) stimulation (SCS) and to i.v. injection of noradrenaline (NA, 125-500 ng kg-1), angiotensin II (Ang II, 40-200 pmol kg(-1), acetylcholine (ACh, 1 nmol kg(-1), calcitonin gene-related peptide (CGRP, 0.1 nmol kg(-1) and sodium nitroprusside (SNP, 5 microg kg-1) were examined in pithed rats. 2.In euglycemic pithed rats, low and medium doses of insulin dose-dependently potentiated vasopressor responses to SCS (2-8 Hz), NA, while higher doses of insulin had little effect on SCS- and NA-induced pressor responses. All doses of insulin significantly augmented pressor responses to Ang II. 3. In pithed rats with artificially increased blood pressure, SCS (2 and 4 Hz) induced a frequency-dependent depressor response, which was blocked by infusion of CGRP(8-37) (CGRP receptor antagonist, 60 nmol kg(-1) min(-1). 4. In euglycemic pithed rats, low-doses of insulin significantly attenuated depressor responses to SCS and CGRP, but medium and high doses of insulin remained unaffected. 5. All doses of insulin significantly inhibited depressor response to ACh, while SNP-induced depressor response was not significantly affected by any doses of insulin. 6. These results suggest that insulin at low and medium concentrations increases adrenergic vasoconstriction, which is partly associated with inhibition of CGRPergic nerve function and endothelium function. It is also suggested that lack of insulin effect at higher concentrations may result from acute desensitization of insulin action, possibly via insulin receptors.
Takatori
Shingo
S
Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
Mizote
Masako
M
Zamami
Yoshito
Y
Kurosaki
Yuji
Y
Kawasaki
Hiromu
H
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D002317:Cardiovascular Agents; D007328:Insulin; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D009638:Norepinephrine