Reduced pulmonary vascular reactivity after cold exposure to acute hypoxia: a role of nitric oxide (NO).
Exposure to high altitude causes pulmonary hypertension and alterations in pulmonary vascular reactivity. Among the environmental factors, cold exposure has been suggested to be involved in the development of pulmonary hypertension. However, little information is available about pulmonary vascular reactivity after cold exposure. We examined whether cold exposure can cause changes in pulmonary vascular reactivity to acute hypoxia and the possible participation of endogenous nitric oxide. We measured mean systemic (Psa) and pulmonary artery pressures (Ppa) in conscious rats after 1-week cold exposure (3.5 +/- 1.0 degrees C). Subsequently, we investigated hypoxic pulmonary vasoconstriction (HPV) with and without endogenous NO inhibition using N(G)-nitro-L-arginine methyl ester (3 mg/kg) or 7-nitroindazole (1 mg/kg). Cold exposure for 1 week caused a small but significant increase in Ppa, but not in Psa. Neither Ppa nor Psa showed significant changes after both NO inhibitions in rats exposed to cold. However, cold exposure caused a blunted HPV and an increase in plasma nitrite-nitrate concentration compared with rats kept in a neutral environment (24.0 +/- 1.0 degrees C). In addition, NO inhibition by N(G)-nitro-L-arginine methyl ester partially restored the blunted HPV in rats exposed to cold, but not 7-nitroindazole, a selective inhibitor of neuronal NO synthase. We concluded that cold exposure alters pulmonary vascular reactivity to acute hypoxia, and augmented endothelial NO bioactivity plays a counterregulatory role in response to acute hypoxia during cold exposure in rats.
Watanabe
Kenya
K
First Department of Internal Medicine, Shimshu University School of Medicine, Matsumoto, Japan.
Koizumi
Tomonobu
T
Ruan
Zonghai
Z
Kubo
Keishi
K
Sakai
Akio
A
Shibamoto
Tadashige
T
D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D003080:Cold Temperature; D006976:Hypertension, Pulmonary / Q000150:complications / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester