1 Urocortin, an endogenous peptide structurally related to corticotropin-releasing factor (CRF), has potent cardiovascular e ects, suggesting that it may be of signi®cance in cardiovascular regulation. The objective of this study was to analyse the e ects of urocortin and its action mechanisms on human blood vessels. 2 To this, 3 mm long segments from human saphenous veins were prepared for isometric tension recording in an organ bath. 3 In the segments at basal resting tone, urocortin did not produce any e ect, but in the segments precontracted with endothelin-1 (1 ± 10 nM), urocortin (1 pM ± 10 nM) produced concentrationdependent relaxation. 4 This relaxation was not modi®ed by the inhibitor of nitric oxide synthase N G -nitro-L-arginine methyl ester (L-NAME, 100 mM), but it was potentiated by the cyclo-oxygenase inhibitor meclofenamate (10 mM) and it was reduced by the inhibitors of high-conductance Ca 2+ -dependent potassium channels tetraethylammonium (TEA, 10 mM) and charybdotoxin (100 nM). 5 These results indicate that human saphenous veins are very sensitive to urocortin, which produces vascular relaxation by a mechanism independent of nitric oxide and dependent of highconductance Ca 2+ -dependent potassium channels, and that it may be opposed by the release of vasoconstrictor prostanoids. Therefore, urocortin may be of signi®cance for regulation of the venous circulation in humans. British Journal of Pharmacology (2002) 136, 90 ± 94

These results suggest that urocortin produces a marked vasodilation of renal arteries, which may be mediated by nitric oxide in females and by activation of potassium channels in both genders, and is reduced by diabetes in renal arteries from females.

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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.