New Insights into the Mechanisms Underlying Vascular and Cardiac Effects of Urocortin

Ignacio      Diaz; Tarik      Smani

doi:10.2174/1570161111311040009

Abstract

Urocortin comprises a group of endogenously produced peptide hormones that belong to the corticotropinreleasing factor (CRF) family with promising future as potential drugs for the treatment of heart disease. Members of the urocortin family are known to act as potent regulators of cardiac and vascular functions, through the activation of the CRF receptors that are highly expressed in heart and peripheral tissues. Urocortin exhibits potent vasodilatory effects in arteries from different species. These effects have been related to its capability to regulate the intracellular Ca2+ concentrations ([Ca2+]i) by different molecular mechanism. Beside, urocortin increases heart contractility and evokes positive inotropic and lusitropic effects by mechanisms involving different kinases signalling pathways. Urocortin peptides have also the ability to protect the heart from ischemia and reperfusion injuries by their improvement of post-ischemic cardiac performances, which include the recovery of heart contraction, the prevention from intracellular Ca2+ overload and the reduction of cardiac cell death. Furthermore, heart protection by urocortin involves the regulation of the transcription of specific genes acting to minimize mitochondrial damage, cell death, and oxidative stress. This review summarizes some of the recent findings related to the molecular mechanism underlying the role of urocortin in both vascular and cardiac function.

Keywords: Urocortin, vascular smooth muscle relaxation, positive inotropism, cardioprotection.

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