Alterations in phenylephrine-induced contractions and the vascular expression of Na+,K+-ATPase in ouabain-induced hypertension

1 Hypertension development, phenylephrine-induced contraction and Na+,K+-ATPase functional activity and protein expression in aorta (AO), tail (TA) and superior mesenteric (SMA) arteries from ouabain- (25 mug day(-1), s.c., 5 weeks) and vehicle-treated rats were evaluated. 2 Ouabain treatment increased systolic blood pressure (127 +/- 1 vs 160 +/- 2 mmHg, n = 24, 35; P < 0.001) while the maximum response to phenylephrine was reduced (P < 0.01) in AO (102.8 +/- 3.9 vs 67.1 +/- 10.1% of KCI response, n = 12, 9) and SMA (82.5 +/- 7.5 vs 52.2 +/- 5.8%, n = 12, 9). 3 Endothelium removal potentiated the phenylephrine response to a greater extent in segments from ouabain-treated rats. Thus, differences of area under the concentration-response curves (dAUC) in endothelium-denuded and intact segments for control and ouabain-treated rats were, respectively: AO, 56.6 +/- 9.6 vs 198.3 +/- 18.3 (n = 9, 7); SMA, 85.5 +/- 15.4 vs 165.4 +/- 24.8 (n = 6, 6); TA, 13.0 +/- 6.1 vs 39.5 +/- 10.4% of the corresponding control AUC (n = 6, 6); P < 0.05. 4 The relaxation to KCI (1 - 10 mM) was similar in segments from both groups. Compared to controls, the inhibition of 0.1 mM ouabain on KCI relaxation was greater in AO (dAUC: 64.8 +/- 4.6 vs 84.0 +/- 5.1%, n=11, 14; P < 0.05), similar in SMA (dAUC: 39.1 +/- 3.9 vs 43.3 +/- 7.8%, n=6, 7; P > 0.05) and smaller in TA (dAUC: 62.1 +/- 5.5 vs 41.4 +/- 8.2%, n=12, 13; P < 0.05) in ouabain-treated rats. 5 Protein expression of both alpha(1) and alpha(2) isoforms of Na+,K+-ATPase was augmented in AO, unmodified in SMA and reduced in TA from ouabain-treated rats. 6 These results suggest that chronic administration of ouabain induces hypertension and regional vascular alterations, the latter possibly as a consequence of the hypertension.