title: eNOS-dependent vascular interaction between nitric oxide and calcitonin gene-related peptide in mice: gender selectivity and effects on blood aggregation.
abstract: The present study was performed to explore a possible vascular interplay between nitric oxide (NO) and calcitonin gene-related peptide (CGRP). We examined factors affecting CGRP release by the NO donor, nitroglycerin (NTG) and the potential involvement of endothelial NO synthase (eNOS) using eNOS knockout (-/-) vs. wild-type (+/+) mice. In the female eNOS (+/+) mice, but not in males, in vitro NTG (0.73 mM) induced significant increases in the release of CGRP-like immunoreactivity (CGRP-LI) from the aorta and the heart but not from the small intestine. In eNOS (-/-) mice, NTG incubation did not induce any CGRP-LI changes in either gender. These results suggest that NTG-induced CGRP release is eNOS-dependent and tissue- and gender-selective. The functional implication of this NO-CGRP interaction was further examined by testing the anti-aggregatory action of acetylcholine (Ach). Ach-induced platelet inhibition was significantly enhanced by the addition of aorta segments of either gender. However, the female aorta segments exhibited a greater platelet inhibitory effect, which could be reversed by the blockade of either CGRP or eNOS. Our study revealed a novel eNOS-dependent interaction between NO and CGRP, and the possible participation of regulatory peptides in affecting platelet function and possibly cardiovascular protection in females.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Woo-In
authors.initials: WI
authors.lastname: Lee
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Fung
authors.forename: Ho-Leung
authors.initials: HL
authors.lastname: Fung
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D005996:Nitroglycerin / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012737:Sex Factors
chemical_list: D020030:Nitric Oxide Donors; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; C058636:calcitonin gene-related peptide (8-37); D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine