Enhanced Na⁺, K⁺-ATPase activity and endothelial modulation decrease phenylephrine-induced contraction in aorta from ouabain-treated normotensive and hypertensive rats.
OBJECTIVE
The purpose of this study was to compare the effect of long-term ouabain treatment on the vascular reactivity and Na+, K+-ATPase activity of a conductance artery from normotensive and hypertensive rats.


METHODS
Male Wistar rats were treated with ouabain (~8.0 µg/day, subcutaneously) or vehicle for 5 and 20 weeks, and spontaneously hypertensive rats (SHRs) for 5 weeks. Vasoconstrictor response to phenylephrine (10-10 to 10-4 M) and relaxation curves to KCl (1-10 mM) were analyzed in thoracic aorta. The effects of endothelial removal, L-NAME (100 μM), and indomethacin (10 μM) were used to evaluate the endothelial, nitric oxide (NO), and cyclooxygenase (COX) modulation of phenylephrine response, respectively. Protein expression of endothelial and neuronal NO synthase (NOS) and COX-2 were also investigated.


RESULTS
The phenylephrine-induced contraction was reduced, whereas the relaxation to KCl was enhanced in the aorta of ouabain-treated Wistar rats and SHRs. In both strains, endothelial modulation of α-adrenergic response was enhanced, related to an increased NO and reduced COX-derived vasoconstrictor factor modulation. Aortas from 20-week ouabain-treated Wistar rats showed reduced COX-2 and enhanced eNOS protein expression. In SHRs, 5-week ouabain treatment reduced COX-2 and increased nNOS protein expression.


CONCLUSIONS
The results suggest that long-term ouabain treatment reduces the α-adrenergic response of aorta from normotensive rats and SHRs, associated with an increase of NO synthesis, reduced COX-2-derived vasoconstrictor factors, and enhanced ouabain-sensitive Na+, K+-ATPase activity. These aortic mechanisms could be adjustments to the elevated blood pressure induced by ouabain, even in the presence of preexisting hypertension.
Ana Paula
AP
Davel
Gisele Kruger
GK
Couto
Camilla Ferreira
CF
Wenceslau
Emilia Cristina
EC
Peres
Fabiano Elias
FE
Xavier
Luciana Venturini
LV
Rossoni
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D010042:Ouabain; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051546:Cyclooxygenase 2; D000254:Sodium-Potassium-Exchanging ATPase