The insulin-mediated vascular and blood pressure responses are suppressed in CGRP-deficient normal and diabetic rats.
BACKGROUND
Calcitonin gene-related peptide (CGRP) is extensively localized in the perivascular or periadventitia nerves throughout the body. CGRP is a potent vasodilator and its release is associated with dilation of these blood vessels. The present study investigated the contribution of the CGRP-mediated vasodilation to the insulin-induced vasodilatory response.


METHODS
Male Wistar rats were treated with capsaicin (50 mg/kg) at 1-3 days of age to ablate the CGRP-containing neurons. After 8 weeks some animals were made diabetic using streptozotocin. Vehicle-treated animals were used as controls. At 12-13 weeks the animals were fasted, anesthetized with chloralose/urethane and instrumented for recording of cardiovascular dynamics.


RESULTS
Body weights and basal, insulin, glucose, mean arterial pressure (MAP), heart rate (HR), and vascular flows were not different in CGRP-deficient rats versus controls. Insulin infusion significantly decreased the MAP in vehicle-treated controls but this response was completely attenuated in CGRP-deficient rats. The decreased response to insulin was associated with a diminished vascular dilatory response in the iliac, renal, and superior mesenteric vessel beds. When insulin was infused in CGRP-deficient diabetic animals there was also a diminished response. Diabetes resulted in an increased renal vascular flow in response to insulin.


CONCLUSIONS
From the present studies we conclude that the insulin-mediated vasodilation was due, in part, to the stimulation of perivascular nerves to release CGRP, and the action of CGRP on vascular smooth muscle enhanced directly or indirectly the vasodilatory response to insulin.
Department of Physiology, Wayne State University School of Medicine, 540 E Canfield, Detroit, MI 48201-1928, USA.
Nahla
N
Salem
Joseph C
JC
Dunbar
D000818:Animals; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency* / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D006339:Heart Rate; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin