title: The hypotensive effect of intrathecally injected (m)VD-hemopressin(α) in urethane-anesthetized rats.
abstract: Previous studies suggest that cannabinoids system plays an important role in cardiovascular regulation. (m)VD-hemopressin(α) (VD-Hpα), an 11-residue peptide originating from the α1 chain of hemoglobin, was recently reported as a selective agonist of cannabinoid CB1 receptor. The present study was undertaken to investigate the intrathecal (i.t.) action of (m)VD-Hpα on blood pressure in urethane-anesthetized rats. Our results demonstrated that injections of (m)VD-Hpα (5-30 nmol, i.t.) produced a dose-dependent decrease in mean arterial pressure (MAP), similar to that of the non-peptidic cannabinoid receptor agonist WIN55212-2 (1.25-10 nmol, i.t.). The hypotensive effect of (m)VD-Hpα was not influenced by the CB1 receptor antagonist AM251 (20 nmol, i.t.) or the CB2 receptor antagonist AM630 (20 nmol, i.t.). However, WIN55212-2-induced hypotension was almost completely prevented by i.t. administration of AM251, not by AM630. The spinal hypotension of (m)VD-Hpα and WIN55212-2 was significantly reduced by pretreatment with the α-adrenoceptor antagonist phentolamine (1 mg/kg, i.v.), but not by the β-adrenoceptor antagonist propranolol (2 mg/kg, i.v.) or the muscarinic receptor antagonist atropine (2 mg/kg, i.v.). In addition, L-NAME (50 mg/kg, i.v.), the inhibitor of nitric oxide (NO) synthase, significantly reduced WIN55212-2-induced hypotension, but had no effect on the hypotensive response to (m)VD-Hpα. Collectively, the results show that i.t. administration of (m)VD-Hpα induces a decrease in MAP via a non-CB1 and non-CB2 mechanism.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
authors.forename: Xu-hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
authors.forename: Zi-long
authors.initials: ZL
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
authors.forename: Jia-xin
authors.initials: JX
authors.lastname: Pan
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
authors.forename: Zheng-lan
authors.initials: ZL
authors.lastname: Han
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Chang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
authors.forename: Hong-hai
authors.initials: HH
authors.lastname: Tang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China. Electronic address: wangrui@lzu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China. Electronic address: fangq@lzu.edu.cn.
authors.forename: Quan
authors.initials: Q
authors.lastname: Fang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007278:Injections, Spinal; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D014520:Urethane / Q000494:pharmacology*
chemical_list: D006454:Hemoglobins; D010446:Peptide Fragments; D043885:Receptor, Cannabinoid, CB2; C473218:hemopressin; D009569:Nitric Oxide; D014520:Urethane
keywords: (m)VD-hemopressin(α); Antagonist; Cannabinoid; Hypotensive response; Rat