Urocortin Protects Coronary Endothelial Function During Ischemia-Reperfusion: A Brief Communication

Abstract

Urocortin is a vasodilator peptide related to corticotrophin-releasing factor, which may protect myocardium during coronary ischemia-reperfusion. To study whether urocortin also protects coronary endothelial function during ischemia-reperfusion, hearts from Sprague-Dawley rats were perfused at constant flow and then exposed to 15 mins ischemia followed by 15 mins reperfusion. In one series of experiments, we found that the coronary relaxation to urocortin (10(-11) to 10(-8) M) was reduced by ischemia-reperfusion (51 +/- 4% vs. 79 +/- 4% of the active tone, for the 10(-10) Mdose). In other series of experiments, we observed that ischemia-reperfusion reduced the coronary relaxation to a test dose of acetylcholine (10(-6) M) (25 +/- 2% vs. 54 +/- 9% of active tone), without modifying the relaxation to sodium nitroprusside (10(-6) M). Treatment with a low threshold concentration of urocortin (10(-11) M), administered before ischemia and during reperfusion, partly improved the coronary relaxation to acetylcholine (36 +/- 3% of active tone). These results suggest that ischemia-reperfusion impairs the coronary vasodilation to urocortin and produces endothelial dysfunction and that this endothelial dysfunction may be improved by urocortin.

Long-Term Effects of Early Overnutrition in the Heart of Male Adult Rats: Role of the Renin-Angiotensin System

“…In controls, ischemia-reperfusion induced a reduction of myocardial contractility, coronary vasoconstriction to angiotensin II and coronary endothelium-dependent vasodilatation to bradykinin. This agrees with previous studies [27], [28], [55], suggesting that this condition may cause injury of myocardial, coronary smooth muscle and endothelial cells, respectively, and this injury was correlated with increased expression of apoptotic markers after ischemia-reperfusion. Although the degree of impairment induced by ischemia-reperfusion on myocardial and coronary function was similar in overfed and control rats, the mechanisms of this impairment may differ.…”

Chronic stress impacts the cardiovascular system: animal models and clinical outcomes

“…In this experiment, pitavastatin upregulated expression of CRH-R1 mRNA, suggesting a role for corticotropin receptors in the vasoprotective effect of this drug. The corticotropin receptor agonist urocortin improves the vasodilatory effect of acetylcholine after ischemic-reperfusion injury (102,192). Increased levels of corticotropin have also been reported after beneficial physical activities (305).…”

Mechanisms of the protective effects of urocortin on coronary endothelial function during ischemia–reperfusion in rat isolated hearts

“…I–R may alter not only myocardial function but also the function of coronary endothelium (Laude et al ., 2001), and this latter phenomenon was also observed in the present study as the coronary relaxation to acetylcholine was reduced in this condition. In a previous study from our laboratory using the same experimental model of I–R (García‐Villalón et al ., 2004), we have found that the coronary relaxation to a endothelium‐independent agent (sodium nitroprusside) is not modified, suggesting that the reduction in the acetylcholine response found in the present study is due to specific impairment of the endothelial function.…”

“…After reperfusion for 15 min, the coronary vascular bed was pre‐constricted by adding U46619 (100–300 n M ) to the perfusion buffer, and then the coronary relaxation to acetylcholine (10 n M –10 μ M ) was recorded. These durations of ischemia and reperfusion were chosen because in a previous study (García‐Villalón et al ., 2004) it was found that they impaired specifically endothelium‐dependent relaxation. Time‐control hearts were perfused during the same total time (45 min) at constant flow before the concentration–response curve to acetylcholine.…”

“…The mechanisms of this protection in the endothelial cells may be similar to or different from those operating in myocardial cells. In a previous study from our laboratory (García‐Villalón et al ., 2004) we have found that urocortin may also be protective of endothelial function, as low concentrations of this peptide improved the coronary relaxation to acetylcholine in perfused rat hearts after I–R. The aim of this study was to further study the mechanisms of this protective action of urocortin on the endothelium.…”