Time course of synergistic interaction between DOCA and salt on blood pressure: roles of vasopressin and hepatic osmoreceptors.
In DOCA-salt rats, the time course of the synergistic interaction between osmolality and DOCA to produce hypertension is unknown. Therefore, in rats 2 wk after implantation of subcutaneous silicone pellets containing DOCA (65 mg) or no drug (sham), we determined blood pressure (BP) and heart rate (HR) responses, using telemetric pressure transducers, during 2 wk of excess salt ingestion (1% NaCl in drinking water). BP was unaltered in sham rats after increased salt, but in DOCA rats BP increased within 4 h. The initial hypertension of 30-35 mmHg stabilized within 2 days, followed approximately 5 days later by a further increment of approximately 30 mmHg. HR first decreased during the dark phase; the second phase was linked to an abrupt increase in HR and BP variability and decreased HR variability. Pressor responses to acute intravenous hypertonic saline infusion were doubled in DOCA-treated rats via vasopressin and nonvasopressin mechanisms. Only in DOCA-treated rats, portal vein hypertonic saline infusion increased BP, which was prevented by V(1) vasopressin blockade. After 2 wk of DOCA-salt, oral ingestion of water rapidly decreased BP. Intraportal infusion of water did not lower BP in DOCA-salt rats, suggesting that hepatic osmoreceptors were not involved. In summary, the hypertension of DOCA-treated rats consuming excess salt exhibits multiple phases and can be rapidly reversed. Hypertonicity-induced vasopressin and nonvasopressin pressor mechanisms that are augmented by DOCA, and hepatic osmoreceptors may contribute to the initial developmental phase. With time, combined DOCA-salt induces marked changes in the regulation of the autonomic nervous system, which may favor hypertension development.
Brooks
Virginia L
VL
Department of Physiology and Pharmacology L-334, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA. brooksv@ohsu.edu
Freeman
Korrina L
KL
Qi
Yue
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D003900:Desoxycorticosterone / Q000008:administration & dosage*; D004347:Drug Interactions; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D014667:Vasopressins / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D017483:Receptors, Vasopressin; D017673:Sodium Chloride, Dietary; D014667:Vasopressins; D003900:Desoxycorticosterone