Effects of calcitonin gene-related peptide on canine cerebral artery strips and the in-vivo vertebral blood flow in dogs.
The effects of calcitonin gene-related peptide (CGRP) on canine cerebral arteries and on vertebral blood flow were investigated in-vivo and in-vitro and the findings compared with the effects of vasoactive intestinal peptide (VIP) and substance P. Administration of CGRP into the vertebral artery caused a dose-dependent and long-lasting increase in blood flow. The in-vivo vasodilatory effects of substance P and VIP were short-lasting. CGRP (0.1 to 100 nmol/l) elicited a concentration-dependent relaxation of the isolated middle cerebral and basilar arteries when the tissues were precontracted by exposure to prostaglandin F2 alpha (PGF2 alpha). This effect was not antagonized by propranolol, atropine, tetrodotoxin, (N-Ac-Tyr1, D-Phe2)-growth hormone-releasing factor(1-29)-NH2 or (D-Pro2, D-Trp7,9) substance P. CGRP also reduced concentration-dependently the contraction of cerebral arteries induced by KCl or 9,11-epithio-11,12-metano-thromboxane A2 (STXA2). Mechanical removal of the endothelium did not abolish the vasodilatory response to CGRP. In PGF2 alpha-contracted canine cerebral arteries, VIP (0.1 to 100 nmol/l) was less potent a vasodilator than CGRP. At low concentrations (0.01 to 1 nmol/l) substance P elicited a rapid and short-lasting relaxation, and in the absence of endothelium this relaxation disappeared. These findings are clear evidence that CGRP modulates vascular tone.
Ikegaki
I
I
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
Suzuki
Y
Y
Satoh
S
S
Asano
T
T
Shibuya
M
M
Sugita
K
K
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001488:Basilar Artery / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014711:Vertebral Artery / Q000187:drug effects
D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D015740:Calcitonin Gene-Related Peptide