Endothelial modulation of ouabain-induced contraction and sodium pump activity in aortas of normotensive Wistar-Kyoto and spontaneously hypertensive rats.
The influence of vascular endothelium on ouabain-induced contractions and sodium pump activity in aortic segments of Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) was analyzed. De-endothelialization increased and reduced ouabain-induced contractions in WKY and SHR segments, respectively. The effects of de-endothelialization were not reproduced by pretreatment of the segments with NG-nitro-L-arginine methyl ester, indomethacin, or 5, 8, 11, 14-eicosatetraenoic acid, acetyl salicylic acid, dazoxiben, phosphoramidon, BQ-123, or superoxide dismutase. Bioassay experiments suggest that ouabain releases a diffusible factor from endothelial cells that inhibits or facilitates digitalis-induced contractions in WKY and SHR segments, respectively. In a potassium-free solution, potassium-induced relaxation in segments of both strains was abolished by ouabain in de-endothelialized aortas and reduced in intact ones. Ouabain-sensitive 86Rb+ uptake was significantly reduced by de-endothelialization both in WKY and in SHR. These results suggest that the vascular endothelium of WKY and SHR aortas releases a diffusible factor that stimulates the sodium pump and/or protects it from ouabain blockade. Ouabain also releases a diffusible endothelium-derived factor in SHR aortas that facilitates ouabain-induced contractions.
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A
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Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, España.
Marín
J
J
Arribas
S
S
González
R
R
Barrús
M T
MT
Salaices
M
M
Sánchez-Ferrer
C F
CF
D000818:Animals; D001011:Aorta; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012414:Rubidium Radioisotopes / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D012414:Rubidium Radioisotopes; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium