Endothelium-dependent effects of substance P and calcitonin gene-related peptide on mouse pial arterioles.
OBJECTIVE
The effects of substance P (SP) and calcitonin gene-related peptide (CGRP) were tested on pial arterioles of mice. This was done because (1) perivascular peptidergic nerves may play an important role in modulation of cerebrovascular responses; (2) there are conflicting data concerning the mechanism of action of CGRP; (3) there are few or no studies directly testing the endothelium dependence of dilation by these peptides in the cerebral circulation; and (4) we wished to extend previous observations of mice by comparing peptidergic responses in the mouse with those published for other species.


METHODS
The pial arterioles were monitored in vivo using video microscopy and image-shearing techniques for measuring diameter. Focal endothelial injury was produced with a laser-Evans blue technique. Responses to SP and CGRP were tested before and after endothelial injury. They were also tested before and during treatment with agents that interfere with responses mediated by endothelium-derived relaxing factor (EDRFACh). They were also tested before and during treatment with indomethacin.


RESULTS
Both CGRP and SP produced dilation that was blocked by endothelial injury and by agents interfering with responses mediated by EDRFACh. Indomethacin had no effect.


CONCLUSIONS
SP and CGRP produce endothelium-dependent dilations. These dilations are probably mediated by EDRFACh. With respect to SP, these results are similar to those reported for other vessels and species. With respect to CGRP, the finding of endothelium dependence has not been previously reported for cerebral vessels. However, very few species have been tested. Reports of other vascular beds in other species sometimes parallel and sometimes contradict our findings with CGRP.
Rosenblum
W I
WI
Department of Pathology (Neuropathology), Virginia Commonwealth University-Medical College of Virginia, Richmond.
Shimizu
T
T
Nelson
G H
GH
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D005070:Evans Blue; D007213:Indomethacin / Q000494:pharmacology; D007834:Lasers; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D010841:Pia Mater / Q000098:blood supply*; D013373:Substance P / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013373:Substance P; D005070:Evans Blue; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D007213:Indomethacin