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This Article Full Text Full Text (PDF) All Versions of this Article: 107/4/1037    most recent 00569.2009v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Grossini, E. Articles by Vacca, G. PubMed PubMed Citation Articles by Grossini, E. Articles by Vacca, G.

Intracoronary intermedin 1–47 augments cardiac perfusion and function in anesthetized pigs: role of calcitonin receptors and β-adrenoreceptor-mediated nitric oxide release

Laboratorio di Fisiologia, Dipartimento di Medicina Clinica e Sperimentale, Facoltà di Medicina e Chirurgia, Università del Piemonte Orientale "A. Avogadro", Novara, Italy

Submitted 27 May 2009 ; accepted in final form 18 August 2009

Systemic intermedin (IMD)1–47 administration has been reported to result in vasodilation and marked hypotension through calcitonin-related receptor complexes. However, its effects on the coronary circulation and the heart have not been examined in vivo. The present study was therefore planned to determine the primary in vivo effect of IMD1–47 on coronary blood flow and cardiac function and the involvement of the autonomic nervous system and nitric oxide (NO). In 35 anesthetized pigs, IMD1–47, infused into the left anterior descending coronary artery at doses of 87.2 pmol/min, at constant heart rate and arterial blood pressure, augmented coronary blood flow and cardiac function. These responses were graded in a further five pigs by increasing the infused dose of IMD1–47 between 0.81 and 204.1 pmol/min. In the 35 pigs, the blockade of cholinergic receptors (intravenous atropine, 5 pigs), -adrenoceptors (intravenous phentolamine, 5 pigs), and β₁-adrenoceptors (intravenous atenolol, 5 pigs) did not abolish the cardiac response to IMD1–47, the effects of which were prevented by blockade of β₂-adrenoceptors (intravenous butoxamine, 5 pigs), NO synthase (intracoronary N-nitro-L-arginine methyl ester, 5 pigs), and calcitonin-related receptors (intracoronary CGRP8–37/AM22–52, 10 pigs). In porcine coronary endothelial cells, IMD1–47 induced the phosphorylation of endothelial NO synthase and NO production through cAMP signaling leading to ERK, Akt, and p38 activation, which was prevented by the inhibition of β₂-adrenoceptors, calcitonin-related receptor complexes, and K⁺ channels. In conclusion, IMD1–47 primarily augmented coronary blood flow and cardiac function through the involvement of calcitonin-related receptor complexes and β₂-adrenoreceptor-mediated NO release. The intracellular signaling involved cAMP-dependent activation of kinases and the opening of K⁺ channels.

adrenergic receptors; coronary blood flow; signaling