Recently, novel
corticotropin-releasing factor-related
peptides, named
urocortin 1, 2, and 3, and a distinct cardiac and peripheral vascular
receptor (corticotropin-releasing factor receptor 2) were described being part of a peripheral
corticotropin-releasing factor system modulating cardiovascular function in response to stress. Vasorelaxation and blood pressure lowering have been reported after acute administration of these
peptides. No data are available on the acute and chronic effects of
urocortin 2 on blood pressure in models of arterial
hypertension. To test these effects, hypertensive
salt-sensitive and normotensive
salt-resistant Dahl rats were randomly assigned to twice-daily applications of
urocortin 2 or vehicle for 5 weeks. Blood pressure, heart rate, and left ventricular dimension and function were recorded at baseline, after initial application, and, together with cardiac and aortic expression of
urocortin 2 and its receptor, after 5 weeks of treatment.
Urocortin 2 significantly reduced blood pressure in hypertensive rats without affecting heart rate. Long-term
urocortin 2 treatment in hypertensive rats induced sustained blood pressure reduction and diminished the development of
hypertension-induced
left ventricular hypertrophy and the deterioration of left ventricular contractile function.
Corticotropin-releasing factor receptor 2 expression was preserved despite chronic stimulation by
urocortin 2. In conclusion, our study shows that, in an animal model of arterial
hypertension,
urocortin 2 has immediate and sustained blood pressure-lowering effects. Beneficial effects on blood pressure, left ventricular dimension, and function, together with preserved receptor expression, suggest that
corticotropin-releasing factor receptor 2 stimulation by
urocortin 2 may represent a novel approach to the treatment of arterial
hypertension.