Positive inotropic effects of carbon monoxide-releasing molecules (CO-RMs) in the isolated perfused rat heart

摘要: Background and purpose: Carbon monoxide (CO) generated by the enzyme haeme oxygenase-1 (HO-1) during breakdown of is known to mediate a number biological effects. Here, we investigated whether CO liberated from two water soluble carbon monoxide-releasing molecules (CO-RMs) exerts inotropic effects on myocardium. Experimental approach: Rat isolated hearts perfused either at constant flow or pressure were used test effect CO-RMs. Key results: CORM-3, fast releaser, produced direct positive when cumulative doses (3, 10 30 μg min−1) single dose (5 μM) infused coronary (CCP) (CCF). The mediated CORM-3 was abolished blockade guanylate cyclase Na+/H+ exchanger, but not inhibitors L-type Ca2+ channels protein kinase C. also caused slight reduction in heart rate did alter flow. In contrast, slow releaser CORM-A1 significant vasodilatation given highest concentration (30 exerted no myocardial contractility rate. Conclusion implications: A rapid release rat hearts, whereas slowly released had vasodilatation. Both cGMP exchange appear be involved this further work needed determine relative contribution each pathway CO-mediated effect. British Journal Pharmacology (2006) 149, 1104–1112. doi:10.1038/sj.bjp.0706939