Role of the sarcolemmal sodium pump in nitroprusside-induced vasodilation of the pulmonary artery.
To elucidate the mechanism of nitrovasodilator-induced pulmonary vasodilation, we examined the role of sodium pump and K+ channels in the relaxant responses of canine pulmonary arterial rings to sodium nitroprusside (SNP) under isometric conditions in vitro. Pretreatment with the sodium pump inhibitor ouabain attenuated the SNP-induced vasodilation of KCI-contracted tissues, so that the maximal relaxation decreased from 90 +/- 7 to 62 +/- 6% (P < 0.01), and the negative logarithm of SNP concentration required to produce a half-maximal effect (pD2) decreased from 5.9 +/- 0.4 to 5.1 +/- 0.4 (P < 0.01). This effect was not altered by mechanical removal of the endothelium. In contrast, pretreatment with K+ channel blockers including iberiotoxin, apamin and glibenclamide did not change the relaxant responses to SNP. Incubation of endothelium-denuded rings with SNP increased ouabain-sensitive 86Rb uptake in a dose-dependent manner, an effect that was inhibited by KT 5823, a cGMP-dependent protein kinase inhibitor. These results suggest that activation of sarcolemmal sodium pump may be involved in the nitrovasodilator-induced cGMP-mediated pulmonary vasodilation, whereas K+ channels may play a less important role in this action.
Tagaya
E
E
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tamaoki
J
J
Nishimura
K
K
Nagai
A
A
D000818:Animals; D004285:Dogs; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology*; D012413:Rubidium / Q000493:pharmacokinetics; D012414:Rubidium Radioisotopes; D012508:Sarcolemma / Q000187:drug effects / Q000502:physiology*; D012680:Sensitivity and Specificity; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D014665:Vasodilator Agents; D009599:Nitroprusside; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium