Effects of neuropeptide Y, calcitonin gene-related peptide, substance P, and capsaicin on cerebral arteries in man and animals.
The smooth-muscle tone of pial, middle, and anterior cerebral arteries from humans, cats, and pigs, respectively, was studied in vitro with respect to the effects of capsaicin and various peptides which are present in local perivascular nerves. Neuropeptide Y (NPY) caused concentration-dependent, potent contractions of the cerebral vessels both in the presence and in the absence of endothelium. In contrast to the response to noradrenaline (NA) and K+, the NPY effect was not altered by changes in the extracellular Ca++ concentration. The relaxant action of the calcium antagonist nifedipine on NPY-evoked contraction of cerebral arteries was not inhibited by a Ca++-deficient medium or by a high-Ca++ medium. Calcitonin gene-related peptide (CGRP), substance P (SP), and capsaicin caused relaxation of precontracted cerebral arteries with an intact endothelium. Calcitonin gene-related peptide was the most potent dilatory agent, and removal of the endothelium did not change the CGRP response. In contrast, the ability of SP to cause relaxation was abolished after removal of the endothelium. Capsaicin, which activates sensory nerves, induced long-lasting relaxation in both the presence and absence of endothelium. In conclusion, in contrast to earlier reported data, the contractile effect of NPY seems to be largely independent of extracellular Ca++, while NA- and K+-induced contractions are dependent on extracellular Ca++. The present results suggest that the relaxant effect of nifedipine on cerebral blood vessels may involve actions other than inhibition of Ca++ influx. The relaxant effect of capsaicin is likely to be induced by release of CGRP rather than SP. The potent effects of these peptides on human pial arteries suggest that neuropeptides may be involved in the control of cerebral blood flow in man.
Mejia
J A
JA
Department of Neurosurgery, Karolinska Hospital, Stockholm, Sweden.
Pernow
J
J
von Holst
H
H
Rudehill
A
A
Lundberg
J M
JM
D000818:Animals; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin / Q000494:pharmacology*; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
D009478:Neuropeptide Y; D009479:Neuropeptides; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium; D002211:Capsaicin; D009638:Norepinephrine