Time Course of Synergistic Interaction Between Doca and Salt on Blood Pressure: Roles of Vasopressin and Hepatic Osmoreceptors.
From: Department of Physiology and Pharmacology L-334, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA. brooksv@ohsu.edu
American journal of physiology. Regulatory, integrative and comparative physiology
- Publish Date: Dec 2006
- ISSN: 0363-6119
- Volume: 291
- Issue: 6
- Pages: R1825-34
- Medium: Print
- Language: English
- Citation (JAMA): Brooks Virginia L, Freeman Korrina L, Qi Yue, et al. Time Course of Synergistic Interaction Between Doca and Salt on Blood Pressure: Roles of Vasopressin and Hepatic Osmoreceptors.. Am. J. Physiol. Regul. Integr. Comp. Physiol. Dec 2006;291:R1825-34
Abstract
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.
Mesh Headings (Keywords): Animals, Blood Pressure, Desoxycorticosterone, Drug Interactions, Liver, Male, Mechanoreceptors, Rats, Rats, Sprague-Dawley, Receptors, Vasopressin, Sodium Chloride, Dietary, Vasopressins, Water-Electrolyte Balance
Check for Full Text / PubMed Unique Identifier (PMID): 16857894
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