Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry
ISSN: 0975-413X
Abstract
Changes in the Vascular Expression of Na+ , K + ATPase and Contractions Generated by Phenylephrine in Ouabain Induced Hypertension
Author(s): Hari Prasad Sonwani*In rats treated with ouabain (25 mg day 71, s.c., 5 weeks) or vehicle, the development of hypertension, contraction produced by phenylephrine and Na+, K+-ATPase functional activity and protein expression were assessed in the Aorta (AO), Tail (TA) and Superior Mesenteric (SMA) arteries. Ouabain therapy raised systolic blood pressure (127+1 vs. 160+2 mmHg, n=24, 35; P50.001), although 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), the maximal response to phenylephrine was decreased (P50.01). In segments from rats treated with ouabain, the phenylephrine response was more strongly enhanced by endothelium ablation. Consequently, for control and ouabain treated rats, the Differences in the Area Under the concentration-response Curves (dAUC) in endothelium-denuded and intact segments 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 as opposed to 39.5+10.4% of the reference AUC (n=6, 6); P50.05. Segments from both groups showed similar relaxation to KCl (1 ± 10 mM). The effects of 0.1 mM ouabain on KCl relaxation were observed in rats administered with ouabain in the following ways: AO (dAUC: 64.8+4.6 vs. 84.0+5.1%, n=11, 14; P50.05), SMA (dAUC: 39.1+3.9 vs. 43.3+7.8%, n=6, 7; P40.05) and TA (dAUC: 62.1+5.5 vs. 41.4+8.2%, n=12, 13; P50.05). Rats treated with ouabain had increased protein expression of both the a1 and a2 isoforms of Na+, K+-ATPase in AO, unchanged in SMA and decreased in TA. Six these findings imply that long term ouabain administration causes both hypertension and possible changes in the vascular system in the affected area.
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