Segmental heterogeneity in the mechanism of sodium nitroprusside-induced relaxation in ovine pulmonary artery

Segmental heterogeneity in relaxation response to nitric oxide (NO) was examined using NO donor sodium nitroprusside (SNP) in second- (medium) and fourth-generation (small) ovine isolated intralobar pulmonary arteries. In vessels precontracted with serotonin, NO donors SNP and S-nitroso-N- acetylpenicillamine (SNAP) were more potent in relaxing medium, in comparison to the small, arteries. Soluble guanylyl cyclase (sGC) inhibitor [1,2,4]oxadiazolo-[4,3-a]quinoxaline-1-one (ODQ 3 μM) caused a profound inhibition of SNP relaxation in small as compared with medium-sized arteries. However, both basal and SNP (10 μM)-stimulated intracellular cyclic guanosine monophosphate (cGMP) content was identical in these 2 arterial segments. The Na⁺,K⁺-ATPase inhibitor ouabain (1 μM) had a marked inhibitory effect on SNP-mediated relaxation in both segments. There was no segmental difference in SNP (10 μM)-stimulated plasma membrane Na ⁺,K⁺-ATPase activity and ouabain-sensitive ⁸⁶Rb-uptake. 4-AP (1 mM), a relatively selective inhibitor of K _v channels, decreased the potency of SNP relaxation by about 10-fold in the medium-sized vessels. On the other hand, 4-AP was without effect on the vasodilator potency of SNP in small vessels. Interestingly, in the presence of 4-AP, SNP was equipotent in dilating both medium (pD₂ = 5.80 ± 0.07; E^max = 84 ± 1.6%, n = 7) and small (pD₂ = 5.74 ± 0.15; E_max = 83 ± 2.5%, n = 7) pulmonary arteries. In conclusion, the results of the present study suggest that K _v channels determine the segmental heterogeneity of NO-mediated relaxation in ovine pulmonary artery.