V1a and V1b vasopressin receptors within the paraventricular nucleus contribute to hypertension in male rats exposed to chronic mild unpredictable stress

Depression is an independent nontraditional risk factor for cardiovascular disease and mortality. The chronic unpredictable mild stress (CMS) rat model is a validated model of depression. Within the paraventricular nucleus (PVN), vasopressin (VP) via V_1aR and V_1bR have been implicated in stress and neurocardiovascular dysregulation. We hypothesized that in conscious, unrestrained CMS rats versus control, unstressed rats, PVN VP results in elevated arterial pressure (MAP), heart rate, and renal sympathetic nerve activity (RSNA) via activation of V_1aR and/or V_1bR. Male rats underwent 4 wk of CMS or control conditions. They were then equipped with hemodynamic telemetry transmitters, PVN cannula, and left renal nerve electrode. V_1aR or V_1bR antagonism dose-dependently inhibited MAP after VP injection. V_1aR or V_1bR blockers at their ED₅₀ doses did not alter baseline parameters in either control or CMS rats but attenuated the pressor response to VP microinjected into PVN by ∼50%. Combined V_1aR and V_1bR inhibition completely blocked the pressor response to PVN VP in control but not CMS rats. CMS rats required combined maximally inhibitory doses to block either endogenous VP within the PVN or responses to microinjected VP. Compared with unstressed control rats, CMS rats had higher plasma VP levels and greater abundance of V_1aR and V_1bR transcripts within PVN. Thus, the CMS rat model of depression results in higher resting MAP, heart rate, and RSNA, which can be mitigated by inhibiting vasopressinergic mechanisms involving both V_1aR and V_1bR within the PVN. Circulating VP may also play a role in the pressor response.