The effects of vasoactive peptide urocortin 2 on hemodynamics in spontaneous hypertensive rat and the role of L-type calcium channel and CRFR2

Abstract

UCN2 can modulate electrical remodeling of the myocardium and hemodynamics in an experimental model of SHR via inhibition of L-type calcium channel and CRFR2 in cardiomyocytes.

Cardiovascular Effects of Urocortin-2: Pathophysiological Mechanisms and Therapeutic Potential

“…They also evidenced an apparent anti-hypertrophic effect of Ucn-2, together with acute positive inotropic effects. In addition to its BP-lowering properties, Ucn-2 produced clear enhancements in diastolic and systolic functions in spontaneously hypertensive rats, suggesting a potential benefit in terms of LV function and geometry in arterial hypertension [77]. In the Langendorff-perfused heart at the stage of hypertension-induced severe HF, Ucn-2 perfusion (5nM during 20 minutes) induced positive inotropic and lusitropic effects, together with coronary blood flow improvement [78].…”

“…In this matter, Meili-Butz, Bühler et al [78] documented the improvement in contractile function seen acutely after Ucn-2 as a consequence of increased SR Ca 2+ load. By its turn, Liu, Liu et al [77] suggested Ucn-2 may relief the Ca 2+ overload characterizing SHR, probably through inhibition of current density through L-type Ca 2+ channels, and this may be a pathway through which it can improve LV geometry and function in this condition.…”

Preclinical Development of Gene Therapy

“…Ucn2 gene transfer increased contractility and relaxation for up to 7 months in normal and failing mouse hearts, through improved Ca 2+ handling and increases in functional proteins, like myosin light chain kinase (189,190). In rat models of hypertension and pulmonary hypertension with subsequent right ventricular failure, Ucn1 and Ucn2 administration increased cardiac function and mitigated ventricular and blood pressure increases, resulting in attenuation of hypertension-induced vascular remodeling and LV hypertrophy (155,167,(193)(194)(195). In an ovine animal model of heart failure administration of Ucns resulted in a range of beneficial dose-dependent cardiovascular and renal effects (164-166).…”