Central Action of Increased Osmolality to Support Blood Pressure in Deoxycorticosterone Acetate–Salt Rats

To test the hypothesis that increased osmolality contributes to hypertension in deoxycorticosterone acetate (DOCA)-salt–hypertensive rats by acting in the brain, DOCA-salt and Sham-salt rats were instrumented with bilateral, nonoccluding intracarotid and femoral catheters. Two weeks prior, rats were uninephrectomized and received subcutaneous implants with or without DOCA (65 mg) and began drinking salt water (1% NaCl and 0.2% KCl). DOCA-salt rats (n=28) exhibited elevated blood pressure (159±4 mm Hg; P<0.05) and heart rate (392±10 bpm; P<0.05) compared with Sham-salt animals (n=5; blood pressure: 107±5 mm Hg; heart rate: 355±10 bpm). Bilateral intracarotid infusion of hypotonic fluid (osmolality: ≈40 mOsm/L), which lowers osmolality of blood to the brain by ≈2%, rapidly decreased blood pressure in DOCA-salt rats (−22±4 mm Hg after 15 minutes; P<0.05; n=7) but not Sham-salt rats (2±2 mm Hg; n=5). Hypotonic fluid infused intravenously did not lower blood pressure (0±2 mm Hg) in DOCA-salt rats (n=7). In DOCA-salt rats pretreated with a V1 vasopressin antagonist (Manning compound, 5 &mgr;g, IV), intracarotid hypotonic infusion still decreased blood pressure (−10±3 mm Hg; P<0.05; n=9), but the response was smaller (P<0.05). Finally, in DOCA-salt rats (n=4) pretreated with the V1 antagonist and the ganglionic blocker hexamethonium, decreasing osmolality of blood to the brain did not reduce blood pressure. These data indicate that, in DOCA-salt rats, hypertonicity acts in the brain to support blood pressure, in part by stimulating vasopressin secretion and in part by stimulating another rapidly reversible mechanism, likely the sympathetic nervous system.