Depression is an independent non-traditional 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 vs 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 four weeks 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 inhibition of vasopressinergic mechanisms involving both V_1aR and V_1bR within the PVN. Circulating VP may also play a role in the pressor response.

中文翻译：

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慢性轻度不可预测压力的雄性大鼠脑室旁核内的V _1a和V _1b血管加压素受体促成高血压

抑郁是心血管疾病和死亡率的独立的非传统危险因素。慢性不可预测的轻度应激（CMS）大鼠模型是一种经过验证的抑郁模型。在室旁核（PVN）内，经由V _1a R和V _1b R的加压素（VP）与压力和神经心血管失调有关。我们假设在有意识的，不受约束的CMS大鼠与对照组，无压力的大鼠中，PVN VP通过激活V _1a R和/或V _1b R导致动脉压（MAP），心率和肾交感神经活动（RSNA）升高。大鼠经历了四个星期的CMS或对照条件。然后为他们配备了血流动力学遥测变送器，PVN套管和左肾神经电极。VVP注射后_1a R或V _1b R拮抗作用剂量依赖性地抑制MAP。ED ₅₀剂量的V _1a R或V _1b R阻滞剂在对照组或CMS大鼠中均未改变基线参数，但使对微注射到PVN中的VP的升压反应减弱了约50％。组合的V 1a _R和V 1b _R抑制作用完全阻断了对照组（而非CMS大鼠）对PVN VP的升压反应。CMS大鼠需要组合最大抑制剂量以阻断PVN内源性VP或对微注射VP的反应。与未受压的对照组相比，CMS大鼠具有更高的血浆VP水平和更高的V _1a R和V _1b丰度PVN中的R转录本。因此，CMS大鼠抑郁模型可导致较高的静息MAP，心率和RSNA，可通过抑制PVN中涉及V _1a R和V _1b R的血管加压素机制来缓解。循环VP也可能在升压反应中起作用。