Chronic ouabain treatment exacerbates blood pressure elevation in spontaneously hypertensive rats: the role of vascular mechanisms

• DOI: 10.1097/hjh.0b013e32832a391f
• Publication Date: 2009-05-21T13:19:14Z
• Authors: Fabiano E Xavier; Ana Paula C Davel; Lívia E Fukuda; Luciana V Rossoni
• Keywords: Male; 0301 basic medicine; Pyridines; Indomethacin; Blood Pressure; In Vitro Techniques; Rats, Inbred WKY; Acetylcholine; Rats; 3. Good health; Vasodilation; Phenylephrine; 03 medical and health sciences; Cyclooxygenase 2; Vasoconstriction; Rats, Inbred SHR; Hypertension; Animals; Cyclooxygenase Inhibitors; Endothelium, Vascular; Thromboxane-A Synthase; Ouabain; Pentanoic Acids

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.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.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.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.