Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 143, Issue 1, Pages 215-225Publisher
WILEY
DOI: 10.1038/sj.bjp.0705919
Keywords
ouabain; hypertension; endothelium; nitric oxide; endothelium-derived hyperpolarizing factor
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1 This study compares the role of endothelial factors in alpha-adrenoceptor contractile responses in mesenteric resistance (MRA) and superior (SMA) mesenteric arteries from ouabain-treated (8.0 mug day(-1), 5 weeks) and untreated rats. The role of the renin - angiotensin system was also evaluated. 2 Ouabain treatment increased systolic blood pressure. In addition, ouabain reduced the phenylephrine response in SMA but did not alter noradrenaline responses in MRA. 3 Endothelium removal or the nitric oxide synthase ( NOS) inhibitor (L-NAME, 100 muM) increased the responses to alpha-adrenergic agonists in both vessels. After ouabain treatment, both endothelial modulation and the L-NAME effect were increased in SMA, while only the L-NAME effect was increased in MRA. Endothelial NOS expression remained unaltered after ouabain treatment. 4 Indomethacin ( 10 muM) similarly reduced the noradrenaline contraction in MRA from both groups; in contrast, in SMA, indomethacin only reduced phenylephrine-induced contractions in segments from untreated rats. Co-incubation of L-NAME and indomethacin leftward shifted the concentration - response curves for noradrenaline more in MRA from ouabain-treated rats; tetraethylammonium (2 mM) shifted the noradrenaline curves further leftward only in MRA from untreated rats. 5 Losartan treatment prevents the development of hypertension but not all vascular changes observed after ouabain treatment. 6 In conclusion, a rise in endothelial NO and impaired prostanoid participation might explain the reduction in phenylephrine-induced contraction in SMA after ouabain treatment. An increase in the modulatory effect of endothelial NO and impairment of endothelium-dependent hyperpolarizing factor effect might explain why the ouabain treatment had no effect on noradrenaline responses in MRA.
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