Vasodilator mechanism of intermedin/adrenomedullin-2 in anesthetized rats.
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.
Abdelrahman
Aly Mohamed
AM
Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman.
Pang
Catherine Cheuk Ying
CC
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
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