title: Effects of endogenous nitric oxide on adrenergic nerve-mediated vasoconstriction and calcitonin gene-related peptide-containing nerve-mediated vasodilation in pithed rats.
abstract: Vascular adrenergic nerves mainly regulate the tone of blood vessels. Calcitonin gene-related peptide-containing (CGRPergic) vasodilator nerves also participate in the regulation of vascular tone. Furthermore, there are nitric oxide (NO)-containing (nitrergic) nerves, which include NO in blood vessels as vasodilator nerves, but it remains unclear whether nitrergic nerves participate in vascular regulation. The present study investigated the role of nitrergic nerves in vascular responses to spinal cord stimulation (SCS) and vasoactive agents in pithed rats. Wistar rats were anesthetized and pithed, and vasopressor responses to SCS and injections of norepinephrine were observed. To evaluate vasorelaxant responses, the BP was increased by a continuous infusion of methoxamine with hexamethonium to block autonomic outflow. After the elevated BP stabilized, SCS and injections of acetylcholine (ACh), sodium nitroprusside (SNP), and CGRP were intravenously administered. We then evaluated the effects of the NO synthase (NOS) inhibitor, N-ω-nitro-L-arginine methylester hydrochloride (L-NAME), on these vascular responses. Pressor responses to SCS and norepinephrine in pithed rats were enhanced by L-NAME, while the combined infusion of L-NAME and L-arginine had no effect on these responses. L-NAME infusion significantly increased the release of norepinephrine evoked by SCS. In pithed rats with artificially increased BP and L-NAME infusion, depressor response to ACh (except for 0.05nmol/kg) was suppressed and SNP (only 2nmol/kg) was enhanced. However, depressor responses to SCS and CGRP were similar to control responses. The present results suggest endogenous NO regulates vascular tone through endothelium function and inhibition of adrenergic neurotransmission, but not through CGRPergic nerves.
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Yamawaki
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan; Department of Pharmacy, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima 770-8503, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Zamami
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan; Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan; Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. Electronic address: stakator@cc.matsuyama-u.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Takatori
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D059331:Adrenergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D062187:Spinal Cord Stimulation; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine
keywords: Acetylcholine chloride (PubChem CID: 6060); Adrenergic nerve-mediated pressor response; Calcitonin gene-related peptide-containing nerve-mediated depressor response; Endogenous nitric oxide; L-NAME (PubChem CID: 39836); L-arginine (PubChem CID: 6322); N-ω-nitro-L-arginine methylester hydrochloride; Pithed rats; Spinal cord stimulation; hexamethonium bromide (PubChem CID: 5938); methoxamine hydrochloride (PubChem CID: 6081); norepinephrine hydrochloride (PubChem CID: 5923); sodium nitroprusside (PubChem CID: 11963622); α-CGRP (PubChem CID: 56841902)