Different modes of sensory neuropeptides and nitric oxide involvement in relaxation of guinea-pig vessels.
This study investigated involvement of calcitonin-gene-related peptide (CGRP), substance P (SP) and nitric oxide (NO) in transmural nerve stimulation (TNS)-induced non-adrenergic, non-cholinergic (NANC) relaxation in isolated guinea pig anterior mesenteric artery (AMA) and posterior caval vein (PCV). Effects of cyclo-oxygenase-generated eicosanoids were blocked with indomethacin (10(-5) M) and so were adrenergic and cholinergic responses with phentolamine (3 x 10(-6) M), propranolol (10(-6) M) and atropine (10(-6) M). In both vessels precontracted by U-46619, TNS induced relaxation, which was almost completely abolished by capsaicin pretreatment (10(-6) M, 15 minutes). In AMA, a CGRP1 receptor antagonist (human CGRP8-37, 10(-5) M) significantly attenuated the relaxation, while did both human CGRP8-37 (10(-5) M) and neurokinin-1 receptor antagonists (spantide, 2 x 10(-5) M and FK888, 3 x 10(-6) M) in PCV. NG-nitro-L-arginine methyl ester (10(-4) M) did not significantly attenuate either the NANC-or CGRP-induced relaxation in AMA. However, it significantly did attenuate both the NANC-and SP-induced relaxation, and it also considerably attenuated CGRP-induced relaxation although insignificantly, in PCV. Thus, CGRP could be significantly responsible for the NO-independent NANC relaxation in AMA, whereas both CGRP and SP could additionally relax PCV in a NO-dependent manner.
Matsuda
H
H
Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka, Japan.
Ohmori
F
F
Uematsu
M
M
Nagata
S
S
Miyatake
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000294:innervation / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004151:Dipeptides; D007211:Indoles; D009479:Neuropeptides; D011450:Prostaglandin Endoperoxides, Synthetic; D017981:Receptors, Neurotransmitter; D014662:Vasoconstrictor Agents; C078949:FK 888; D009569:Nitric Oxide; D013373:Substance P; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C042867:spantide; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester