Relaxation of sheep cerebral arteries by vasoactive intestinal polypeptide and neurogenic stimulation: inhibition by L-NG-monomethyl arginine in endothelium-denuded vessels.
1. Perivascular nerves of the sheep middle cerebral artery show immunoreactivity for both vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP). 2. Rings of endothelium-denuded sheep middle cerebral artery precontracted with 5-hydroxytryptamine were relaxed by CGRP (maximum relaxation = 87.8 +/- 8.1%, pD2 = 7.81 +/- 0.12, n = 12) and by VIP (maximum relaxation = 55.1 +/- 4.1%, pD2 = 7.65 +/- 0.04, n = 18). Rings of endothelium-denuded cat middle cerebral artery precontracted with U46619 were also relaxed by vasoactive intestinal polypeptide (maximum relaxation = 53.1 +/- 6.1%, pD2 = 7.82 +/- 0.11, n = 6). 3. Haemolysate (1 microliters ml-1) inhibited VIP-induced relaxation in endothelium-denuded sheep and cat middle cerebral artery (n = 6) but had no effect on the CGRP-induced relaxation of the sheep middle cerebral artery (n = 6). 4. The relaxant response to VIP in endothelium-denuded sheep middle cerebral artery was inhibited by methylene blue (10 microM) and augmented by either M&B 22948 (10 microM) or superoxide dismutase (150 units ml-1). Indomethacin (1 microM) had no effect. 5. The addition of L-NG-monomethyl arginine (100 microM) inhibited both neurogenic and VIP-induced relaxation of endothelium-denuded sheep MCA by 56 +/- 6% and 60 +/- 6% (n = 5) respectively. The CGRP-induced relaxation was unaffected. 6. It is concluded that neurally mediated vasodilatation in the sheep middle cerebral artery is mediated largely by VIP through a direct action on smooth muscle through a cyclic-GMP-mediated mechanism that appears to involve synthesis of nitric oxide from L-arginine. Vasodilatation by CGRP, which is also contained in perivascular nerves, does not utilize this pathway.
Department of Physiology & Pharmacology, University of Strathclyde, Glasgow.
A J
AJ
Gaw
J
J
Aberdeen
P P
PP
Humphrey
R M
RM
Wadsworth
G
G
Burnstock
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D012756:Sheep; D014660:Vasoactive Intestinal Peptide / Q000032:analysis / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide