The purpose of this study was to compare the effects of an acute stressor (restraint) versus a chronic stressor (social isolation) on the expression of mRNAs for corticotropin-releasing hormone receptor type 2 (CRH-R2) and urocortin 1 (Ucn 1) and urocortin 2 (Ucn 2) in the cardiovascular system of socially monogamous prairie voles of both sexes. Acute restraint for 1 h was followed by a marked increase in plasma corticosterone, and when the animals were re-paired for 1 day, the increment of corticosterone was normalized. However, following chronic social isolation for 4 weeks, plasma corticosterone did not differ significantly from the levels measured in animals living in pairs. Restraint or isolation significantly decreased CRH-R2 mRNA in ventricle, atria, and aorta; however, when these animals were re-paired for 1 day, the modulation of CRH-R2 mRNA was normalized in restraint but not in isolated animals. Restraint stress increased the Ucn 1 mRNA expression in the heart of female and male prairie voles, and when the animals were re-paired, the modulation of Ucn 1 mRNA expression was normalized. However, chronic isolation showed no effect on cardiac Ucn 1 mRNA expression. Although acute restraint stress produced no effect on the cardiac Ucn 2 mRNA expression, chronic isolation was followed by an increased heart Ucn 2 mRNA expression in both sexes. When the isolated animals were re-paired for 1 day, the cardiac Ucn 2 mRNA expression remained upregulated. The results of the present study reveal that acute restraint as well as social isolation can have significant consequences for the modulation of gene expression for the CRH-R2 and the urocortin peptides in cardiovascular tissue in female and male prairie voles.