title: Vasodilator mechanism of intermedin/adrenomedullin-2 in anesthetized rats.
abstract: We examined whether the vasodepressor effect of intermedin/adrenomedullin-2, a new member of the calcitonin gene-related peptide family, acted via activation of the nitric oxide/L-arginine pathway, the prostanoid pathway, or the opening of K+ channels. Intermedin/adrenomedullin-2 (0.3-30 nmol/kg) dose-dependently decreased mean arterial pressure (ED50 of 2.3 +/- 0.69 nmol/kg) and increased heart rate in anesthetized rats. The depressor effect of intermedin/adrenomedullin-2 (3 nmol/kg, ED70 dose) was unaffected by pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, inhibitor of NO synthase, 50 mg/kg i.v.), indomethacin (cyclooxygenase inhibitor, 10 mg/kg i.v.), tetraethylammonium (TEA, nonspecific K(+)-channel blocker; 60 mg/kg i.v.) or the respective vehicle. Pretreatment with mecamylamine (ganglionic blocker, 10 mg/kg i.v.) augmented the depressor response and abolished the tachycardic effect of intermedin/adrenomedullin-2 (3 nmol/kg). Therefore, the depressor effect of intermedin/adrenomedullin-2 is not mediated via the nitric oxide/L-arginine pathway, production of prostanoids or opening of TEA-sensitive K+ channels, but is opposed by activity of the sympathetic nervous system. Its tachycardic effect is mediated via the baroreflex mechanism.
authors.affiliation: Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman.
authors.forename: Aly Mohamed
authors.initials: AM
authors.lastname: Abdelrahman
authors.forename: Catherine Cheuk Ying
authors.initials: CC
authors.lastname: Pang
mesh_terms: D053607:Adrenomedullin / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D014665:Vasodilator Agents
chemical_list: C499411:Adm2 protein, rat; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D018733:Nicotinic Antagonists; D026902:Potassium Channel Blockers; D011453:Prostaglandins; D014665:Vasodilator Agents; D053607:Adrenomedullin; D009569:Nitric Oxide; D019789:Tetraethylammonium; D008464:Mecamylamine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin