Grossini E, Molinari C, Mary DA, Uberti F, Caimmi PP, Vacca G
Intracoronary intermedin 1-47 augments cardiac perfusion and function in anesthetized pigs. Role of calcitonin receptors and {beta}-adrenergic-nitric oxide release. [JOURNAL ARTICLE]
J Appl Physiol 2009 Aug 20.
Systemic intermedin1-47 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 intermedin1-47 on coronary blood flow and cardiac function and the involvement of autonomic nervous system and of nitric oxide (NO). In 35 anesthetized pigs, intermedin1-47, 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 intermedin1-47 between 0.81-204.1 pmol/min. In the 35 pigs the blockade of cholinergic receptors (intravenous atropine; 5 pigs), of alpha-adrenoceptors (intravenous phentolamine; 5 pigs) and of beta1-adrenoceptors (intravenous atenolol; 5 pigs) did not abolish the cardiac response to intermedin1-47, the effects of which were prevented by blockade of beta2-adrenoceptors (intravenous butoxamine; 5 pigs), nitric oxide synthase (intracoronary L-NAME; 5 pigs), and calcitonin-related receptors (intracoronary CGRP8-37/AM22-52; 10 pigs). In porcine coronary endothelial cells intermedin1-47 induced the phosphorylation of eNOS and NO production through cAMP signaling leading to ERK, Akt and p38 activation, which was prevented by the inhibition of beta2-adrenoceptors, calcitonin-related receptor complexes and potassium channels. In conclusion, intermedin1-47 primarily augmented coronary blood flow and cardiac function through the involvement of calcitonin-related receptor complexes and beta2-adrenoreceptor-mediated NO release. The intracellular signaling involved a cAMP-dependent activation of kinases and the opening of potassium channels. Key words: adrenergic receptors, coronary blood flow, intermedin, nitric oxide.
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