Affiliation:
1. Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan
2. John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan
3. Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan
Abstract
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 V1aR and V1bR 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 V1aR and/or V1bR. 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. V1aR or V1bR antagonism dose-dependently inhibited MAP after VP injection. V1aR or V1bR 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 V1aR and V1bR 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 V1aR and V1bR 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 V1aR and V1bR within the PVN. Circulating VP may also play a role in the pressor response.
Funder
U.S. Department of Veterans Affairs
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology
Cited by
11 articles.
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