Effect of monomeric adiponectin on cardiac function and perfusion in anesthetized pig

Adiponectin, the most abundant adipokine released by adipose tissue, appears to play an important role in the regulation of vascular endothelial and cardiac function. To date, however, the physiological effects of human monomeric adiponectin on the coronary vasculature andmyocardial systo-diastolic function, as well asonparasympathetic/sympathetic involvement and nitric oxide (NO) release, have not yet been investigated. Thus, weplanned to determine the primary in vivo effects of human monomeric adiponectin on coronary blood flow and cardiac contractility/relaxation and the related role of autonomic nervous system, adiponectin receptors, and NO. In 30 anesthetized pigs, human monomeric adiponectin was infused into the left anterior descending coronary artery at constant heart rate and arterial bloodpressure, and the effectsoncoronary bloodflow, left ventricular systo-diastolic function, myocardial oxygen metabolism, and NO release were examined. The mechanisms of the observedhemodynamic responses were also analyzed by repeating the highest dose of human monomeric adiponectin infusion after autonomic nervous systemand NO blockade, and after specific adiponectin 1 receptor antagonist administration. Intracoronary human monomeric adiponectin caused dose-related increases of coronary blood flowand cardiac function. Those effects were accompanied by increased coronary NO release and coronary adiponectin levels. Moreover, the vascular effects of the peptide were prevented by blockade of β₂-adrenoceptors and NO synthase, whereas all effects of human monomeric adiponectin were prevented by adiponectin 1 receptor inhibitor. In conclusion, human monomeric adiponectin primarily increased coronary blood flow and cardiac systo-diastolic function through the involvement of specific receptors, β₂-adrenoceptors, and NO release.