Ouabain-induced hypertension alters the participation of endothelial factors in alpha-adrenergic responses differently in rat resistance and conductance mesenteric arteries.
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 microg 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 microm) 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 microm) 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.
Xavier
Fabiano E
FE
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
Rossoni
Luciana V
LV
Alonso
María J
MJ
Balfagón
Gloria
G
Vassallo
Dalton V
DV
Salaices
Mercedes
M
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D010042:Ouabain; D011189:Potassium Chloride; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine