Acute <scp> V _1b </scp> vasopressin receptor antagonism ameliorates cardiovascular parameters in ovariectomized female rats subjected to chronic mild unpredictable stress

Depression is a recognized non-traditional risk factor for adverse cardiovascular disease (CVD) outcomes. The risk for CVD increases in women after menopause. The chronic mild unpredictable stress (CMS) paradigm is a validated rodent model of depression. In male rats, CMS results in higher blood pressure and sympathoexcitation that is mitigated by direct inhibition of the vasopressin V_1b receptor (V_1bR) within the paraventricular nucleus. In the present study we tested the hypothesis that ovariectomized (OVX) but not gonadally intact female rats display cardiovascular responses similar to male CMS rats and that these responses will be mitigated by systemic V_1b R inhibition. Intact and OVX female rats and male rats were subjected to a 4-week CMS protocol or standard housing (control). Hemodynamics were assessed by telemetry. Left ventricular (LV) function and aortic pulse wave velocity (aPWV) were assessed 1 h after either vehicle or nelivaptan, 10 mg/kg i.p. mean arterial pressure and heart rate were similar in gonadally intact control and CMS female rats but were significantly elevated from baseline values in CMS OVX and male rats. aPWV was elevated in CMS male and OVX rats and improved after treatment with nelivaptan independent of blood pressure. Neither systolic nor diastolic LV function was impaired; however, V_1bR inhibition increased LF ejection fraction in gonadally intact female rats. These findings support the concept that OVX females display cardiovascular responses similar to male rats when subjected to CMS. Systemic V_1b R antagonism ameliorates aortic compliance in both male and OVX rats.