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Alterations in phenylephrine‐induced contractions and the vascular expression of Na + ,K + ‐ATPase in ouabain‐induced hypertension
Author(s) -
Rossoni Luciana V,
Salaices Mercedes,
Marín Jesús,
Vassallo Dalton V,
Alonso María J
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704501
Subject(s) - phenylephrine , ouabain , endocrinology , medicine , chemistry , contraction (grammar) , endothelium , mesenteric arteries , aorta , blood pressure , sodium , artery , organic chemistry
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. 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 KCl response, n =12, 9) and SMA (82.5±7.5 vs 52.2±5.8%, n =12, 9). 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. The relaxation to KCl (1 – 10 m M ) was similar in segments from both groups. Compared to controls, the inhibition of 0.1 m M ouabain on KCl 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. Protein expression of both α 1 and α 2 isoforms of Na + ,K + ‐ATPase was augmented in AO, unmodified in SMA and reduced in TA from ouabain‐treated rats. These results suggest that chronic administration of ouabain induces hypertension and regional vascular alterations, the latter possibly as a consequence of the hypertension.British Journal of Pharmacology (2002) 135 , 771–781; doi: 10.1038/sj.bjp.0704501