title: Chronic ouabain treatment exacerbates blood pressure elevation in spontaneously hypertensive rats: the role of vascular mechanisms.
abstract: OBJECTIVE
  Hypertensive rats are more sensitive to the pressor effects of acute ouabain than normotensive rats. We analyzed the effect of chronic ouabain (approximately 8.0 microg/day, 5 weeks) treatment on the blood pressure of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats and the contribution of vascular mechanisms.
  
  
  METHODS
  Responses to acetylcholine and phenylephrine were analyzed in isolated tail arteries. Protein expression of endothelial nitric oxide synthase and cyclooxygenase-2 (COX-2) were also investigated.
  
  
  RESULTS
  Ouabain treatment enhanced blood pressure only in SHRs. The pD2 for acetylcholine was decreased in arteries from SHRs compared with Wistar-Kyoto rats, and ouabain did not change this parameter. However, ouabain was able to increase the pD2 to phenylephrine in SHRs. Nitric oxide synthase inhibition with NG-nitro-L-arginine methyl ester or potassium channel blockade by tetraetylamonium increased the response to phenylephrine in SHRs, with a smaller increase in response observed in ouabain-treated SHRs. In addition, indomethacin (a COX inhibitor) and ridogrel (a thromboxane A2 synthase inhibitor and prostaglandin H2/thromboxane A2 receptor antagonist) decreased contraction to phenylephrine in tail rings from ouabain-treated SHRs. Protein expression of endothelial nitric oxide synthase was unaltered following ouabain treatment in SHRs, whereas COX-2 expression was increased.
  
  
  CONCLUSIONS
  Chronic ouabain treatment further increases the raised blood pressure of SHRs. This appears to involve a vascular mechanism, related to a reduced vasodilator influence of nitric oxide and endothelium-derived hyperpolarizing factor and increased production of vasoconstrictor prostanoids by COX-2. These data suggest that the increased plasma levels of ouabain could play an important role in the maintenance of hypertension and the impairment of endothelial function.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, Brazil.
authors.forename: Fabiano E
authors.initials: FE
authors.lastname: Xavier
authors.forename: Ana Paula C
authors.initials: AP
authors.lastname: Davel
authors.forename: Lívia E
authors.initials: LE
authors.lastname: Fukuda
authors.forename: Luciana V
authors.initials: LV
authors.lastname: Rossoni