Time course of synergistic interaction between DOCA and salt on blood pressure: Roles of vasopressin and hepatic osmoreceptors

Virginia L. Brooks, Korrina L. Freeman, Yue Qi

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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 ∼5 days later by a further increment of ∼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 V1 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.

Original languageEnglish (US)
Pages (from-to)R1825-R1834
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number6
StatePublished - 2006
Externally publishedYes


  • Heart rate
  • Hypertension
  • Hypertonic saline
  • Osmolality
  • Rats
  • Telemetry

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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