NISHIURA Naoki Dept. of Cardiac Physiol., National Cardiovascular Center Research Institute, staff, 心臓生理部, 室員 (70132933)
SHIMOUCHI Akito Dept. of Cardiovascular Dynamics., National Cardiovascular Center Research Institute, staff, 循環動態機能部, 室員 (80211291)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 2000 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1999 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1998 : ¥700,000 (Direct Cost : ¥700,000)
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
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