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

Abstract

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 μg 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 KC1 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 KC1 (1-10 mM) was similar in segments from both groups. Compared to controls, the inhibition of 0.1 mM ouabain on KC1 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 α1 and α2 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.