Urocortin‐2 induces vasorelaxation of coronary arteries isolated from patients with heart failure

Abstract

Summary 1. Urocortin‐2 (Ucn2) is a vasoactive peptide belonging to the corticotrophin‐releasing factor (CRF) family that has potent cardiovascular actions. It has been suggested that Ucn2 participates in the pathophysiology of heart failure. However, little is known about the mechanisms underlying the action of Ucn2 in human coronary arteries. The aim of the present study was to assess the effects of Ucn2 on the vascular tone of human coronary arteries dissected from heart failure patients. 2. Human coronary arteries were dissected from the hearts of patients subjected to orthotopic heart transplantation. Coronary arteries were obtained from 17 patients with heart failure due to dilated cardiomyopathy of ischaemic origin in Stage III–IV of the New York Heart Association classification. Changes in tone were measured in arterial rings using force transducers. 3. Application of increasing concentrations of Ucn2 (5–20 nmol/L) to arterial rings precontracted with agonists induced dose‐dependent relaxation of the coronary artery, which was independent of endothelial cell activation. Furthermore, the inhibition of the adenylyl cyclase by MDL‐12 (100 nmol/L) and protein kinase A (PKA) by H89 (1 μmol/L) prevented Ucn2‐mediated relaxation of coronary artery rings. 4. The results of the present study suggest that, in heart failure patients, Ucn2 could be useful in modulating coronary artery circulation independent of endothelial integrity through mechanisms that involve adenylyl cyclase activation and PKA stimulation. The findings warrant further investigation of the role of Ucn2 in circulatory regulation and its potential therapeutic application in heart disease.

Urocortin 2 in cardiovascular health and disease

“…Pronounced falls in systemic arterial pressure were also seen with higher doses of Ucn-2 [6]. Ucn-2 also induced vasorelaxation of coronary arteries isolated from patients with heart failure, independently of endothelial integrity [64].…”

Urocortin 3 expression at baseline and during inflammation in the colon: Corticotropin releasing factor receptors cross-talk

“…Exogenous Ucn1 significantly ameliorates colonic inflammation in a murine model of Crohn’s colitis, which is accompanied by decreased mRNA expression of inflammatory cytokines including TNF-α and IL-6 [13]. Urocortin2 (Ucn2) is a potent immunomodulator and a vasodilator that induces vascular relaxation and has positive effects on the heart via CRF 2 , thus providing protection against heart failure [1,41]. Ucn2 and its high-affinity receptor CRF 2 are expressed in the GI tract under basal conditions and during Crohn’s colitis [4].…”

The Corticotropin Releasing Factor System in the Kidney: Perspectives for Novel Therapeutic Intervention in Nephrology

“…Urocortin 2 is strongly expressed in heart and vessels and shows a robust vasodilatory action in human tissues, particularly in intramyocardial vessels, in internal mammary arteries, and in coronary arteries in vitro through CRF‐R2 stimulation . Urocortin 2 infusion in healthy humans led to a hemodynamic response similar to that observed in experimental heart failure, namely it increased cardiac output, ejection fraction, and heart rate, while it reduced peripheral vascular resistance.…”