The hypotensive effect of intrathecally injected (m) VD-hemopressin(α) in urethane-anesthetized rats

Previous studies suggest that cannabinoids system plays an important role in cardiovascular regulation. (m)VD-hemopressin(alpha) (VD-Hp alpha.), an 11-residue peptide originating from the alpha(1) chain of hemoglobin, was recently reported as a selective agonist of cannabinoid CB1 receptor. The present study was undertaken to investigate the intrathecal (it.) action of (m)VD-Hp alpha on blood pressure in urethane-anesthetized rats. Our results demonstrated that injections of (m)VD-Hp alpha (5-30 nmol, Lt.) 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, Lt.). The hypotensive effect of (m)VD-Hpei was not influenced by the 031 receptor antagonist AM251 (20 nmol, Lt.) or the CB2 receptor antagonist AM630 (20 nmol, it.). However, WIN55212-2-induced hypotension was almost completely prevented by it. administration of AM251, not by AM630. The spinal hypotension of (m)VD-Hpee. and WIN55212-2 was significantly reduced by pretreatment with the ce.-adrenoceptor antagonist phentolamine (1 mg/kg, iv.), but not by the p-adrenoceptor antagonist propranolol (2 mg/kg, iv.) or the muscarinic receptor antagonist atropine (2 mg/kg, iv.). In addition, L-NAME (50 mg/kg, iv.), the inhibitor of nitric oxide (NO) synthase, significantly reduced WIN55212-2-induced hypotension, but had no effect on the hypotensive response to (m)VD-Hpa. Collectively, the results show that it. administration of (m)VD-Hpei induces a decrease in MAP via a non-CB1 and non-CB2 mechanism. (C) 2014 Elsevier Inc. All rights reserved.