Temporal increase in the reactivity of pulmonary vasculature to substance P in chronically hypoxic rats.
We previously demonstrated that the pulmonary vascular response to substance P (SP) increased in chronically hypoxic rats. This study explored the temporal increase in reactivity of the pulmonary vascular response to SP and its underlying mechanisms. First, young female Wistar rats were exposed to sea level (SL) or simulated high altitude (HA) for 15 h/day for 3 days, 1 wk, 2 wk, and 4 wk. Lungs were isolated and perfused with 4% bovine serum albumin in Krebs-Henseleit buffer solution. SP (1.5 x 10(-4) M) induced significant increases in pulmonary arterial pressure (P(pa)), venous pressure (P(v)), capillary pressure (P(c)), arterial resistance (R(a)), and filtration coefficient (K(fc)) in SL lungs. Increases in P(pa) and R(a) were significantly augmented in HA lungs, with a temporal increase trend peaking at 2 wk of HA exposure. The selective neurokinin (NK) type 1 (NK1) receptor antagonist SR-14033 significantly attenuated SP-induced increases in P(pa), P(v), P(c), R(a), and K(fc) in SL lungs. In lungs exposed to HA for 2 wk, SR-14033 suppressed the effect of SP on P(pa). Also, chronic hypoxia induced significant increases in NK1 receptors and NK1 receptor mRNA, with a temporal trend. We conclude that chronic hypoxia temporally augments SP-induced vascular responses, which are closely associated with increases in NK1 receptors and gene expression.
Lai
Yih-Loong
YL
Department of Physiology, National Taiwan University College of Medicine, Taipei 100, Taiwan. tiger@ha.mc.ntu.edu.tw
Chu
Szu-Jung
SJ
Ma
Ming-Chieh
MC
Chen
Chau-Fong
CF
D000531:Altitude; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D002196:Capillaries / Q000503:physiopathology; D002908:Chronic Disease; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D010880:Piperidines / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011812:Quinuclidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D013373:Substance P / Q000494:pharmacology*; D013997:Time Factors
D010880:Piperidines; D011812:Quinuclidines; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C085215:SR 140333; D013373:Substance P