Segmental differences in the mechanism of vascular tone regulation along the serially-connected pulmonary vessels in vivo

本研究旨在探讨从导管到阻力段的活体串联肺血管血管张力调节机制的节段性差异。为此，我们在麻醉猫和大鼠上用X射线电视系统直接测量了一氧化氮合酶(NOS)抑制剂和K~(++)通道对阻力动脉(RA)和导管动脉(CA)内径(ID)的影响。急性低氧暴露诱导的ID收缩位于猫小叶内100-600μm血管，最大反应发生在200-300μμm RA。这种反应模式是低氧所特有的，因为吸入一氧化氮(NO)和前列环素会在更宽的ID范围(100-1000…m)引起肺血管ID反应。在常氧条件下，非选择性抑制一氧化氮合酶引起的CA ID收缩比RA大。在低氧暴露中，inh胆汁淤积者小叶内HPV增强。电压依赖性K~+(K_V)通道抑制使CA和RA的ID收缩几乎一致，而Ca~(2+)敏感的K~(++)通道或ATP敏感的K~(++)通道抑制引起CA的显著收缩和RA的轻微收缩。K&lt；ATP；通道抑制对上述缺氧性反应均无影响。结果表明，在所有动脉中，K_V通道调节基础张力，而NOS和K_lt；Ca&Gt；和K_&lt；ATP&gt；通道主要调节Ca值。通道介导的收缩：在低氧暴露4wk的大鼠中，由于非选择性NOS抑制引起的ID收缩在RA中增强，而在CA中没有。在RA的所有分支中都观察到增强。只有大约50%的RA由于iNOS选择性抑制引起的ID收缩增强。nNOS选择性抑制没有作用。缺氧4周后，eNOS阳性RA的百分率从50%增加到95%，而iNOS的阳性RA百分率仅从10%增加到50%。结果提示，在慢性低氧状态下，eNOS介导的基础张力调节在所有RA中均增强，但在其分支中有零星的iNOS调节。提示HPV阳性的RA和HPV阴性的CA，其血管张力调节机制可能存在明显差异。较少

This study was conducted to investigate segmental differences in the mechanism of vascular tone regulation along the in vivo serially-connected pulmonary vessels, from conduit to resistance segments. To this end, we directly measured effects of inhibitors of nitric oxide synthase (NOS) and K^+ channel on the internal diameter (ID) of resistance arteries (RA) and conduit arteries (CA), using an X-ray television system on anesthetized cats and rats. Moreover, immunohistochemistry analysis for NOS protein was also conducted.Acute hypoxic exposure-induced ID constriction (HPV) was localized in intralobular 100-600μm vessels in the cat, the maximum response being in 200-300μm RA.This response pattern was specific for hypoxia, since inhalations of nitric oxide (NO) and prostacyclin caused ID responses in pulmonary vessels with a more extensive ID range (100-1000μm).In normoxic cats, non-selective NOS inhibition caused a larger ID constriction in CA than in RA.During hypoxic exposure, the inh … More ibition enhanced HPV within the lobule. Voltage-dependent K^+ (K_v) channel inhibition caused almost uniform ID constriction in both CA and RA during normoxia, but Ca^<2+>-sensitive K^+ (K_<Ca>) channel or ATP-sensitive K^+ (K_<ATP>) channel inhibition caused a great constriction in CA and a slight constriction in RA.Under K_<Ca> channel inhibition, hypoxia induced a significant ID constriction also in smaller CA and HPV in RA was slightly enhanced. K_<ATP> channel inhibition had no effect on any of the hypoxic responses. The results suggest that K_V channels regulate basal tone in all arteries, whereas NOS and K_<Ca> and K_<ATP> channels chiefly regulate CA.The data also suggest that HPV in RA is almost independent of K_<Ca> and K_<ATP> channels, whereas the hypoxic CA response depends on the balance between the hypoxia-induced constriction and K_<Ca> channel-mediated dilatation.In rats with 4-wk hypoxic exposure, the ID constriction due to nonselective NOS inhibition was enhanced in RA, but not in CA.The enhancement was observed in all branches of RA.The ID constriction due to iNOS selective inhibition was enhanced only in 〜50% of RA.nNOS selective inhibition had no effect. The percentage of eNOS-positive RA increased to 95% (from 50%) in response to 4-wk hypoxia, but that for iNOS only to 50% (from 10%). The data suggest that eNOS mediated basal tone regulation is enhanced in all RA during chronic hypoxia, but that for iNOS sporadically among their branches. Such NOS upregulation may contribute to attenuating HPV and in turn, inhibit the pulmonary hypertension progress.Together, it is suggested that NOS- and K^+ channel-mediated mechanisms of vascular tone regulation significantly differ between the HPV-positive RA and HPV-negative CA. Less