Neurogenic nitric oxide release increases in mesenteric arteries from ouabain hypertensive rats.

OBJECTIVES We investigated whether chronic ouabain treatment changes the vasoconstrictor responses induced by electrical field stimulation (EFS) in endothelium-denuded rat superior mesenteric arteries and a possible role of neuronal nitric oxide (NO). METHOD Mesenteric arteries from untreated and ouabain-treated rats (approximately equal to 8.0 microg/kg per day, for 5 weeks) were used in this study. Vascular reactivity was analyzed by isometric tension recording. Expression of the neuronal NO synthase isoform was analyzed by Western blot. Noradrenaline release was evaluated in segments incubated with [H]noradrenaline. RESULTS Systolic (SBP) and diastolic (DBP) blood pressure were higher in ouabain-treated rats than in untreated rats (SBP, untreated: 120 +/- 3.5 mmHg versus ouabain-treated: 150 +/- 4.7 mmHg, P < 0.01; DBP, untreated: 87 +/- 3.0 mmHg versus ouabain-treated: 114 +/- 2.6 mmHg, P < 0.001). EFS-induced vasoconstrictions were smaller in arteries from ouabain-treated rats than in those from untreated animals, while the EFS-induced [H]noradrenaline release and the vasoconstriction induced by exogenous noradrenaline (1 nmol/l-10 micromol/l) remained unmodified. The non-selective NO synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (100 micromol/l), increased the EFS-induced vasoconstriction in mesenteric arteries from both groups, although the effect was more pronounced in segments from ouabain-treated rats. The selective neuronal NOS inhibitor, 7-nitroindazole (7-NI; 100 micromol/l) increased EFS-induced contraction only in segments from ouabain-treated rats. Neuronal NOS expression was greater in the mesenteric arteries from ouabain-treated rats than in those from untreated animals. Sodium nitroprusside (0.1 nmol/l-10 micromol/l) induced a similar vasodilatation in segments from both groups. CONCLUSIONS These results suggest that chronic ouabain treatment is accompanied by an increase in neuronal NO release that reduces EFS-induced vasoconstriction.