Effects of inhaled prostacyclin analogue on chronic hypoxic pulmonary hypertension.
Inhaled PGI2 has been reported to elicit pulmonary vasodilation, but whether it is also effective in treating chronic hypoxic pulmonary hypertension is still uncertain. We designed this study to address the in vivo effectiveness of inhaled Beraprost, a stable PGI2 analogue, on pulmonary vascular tone during hypoxic exposure in normoxic (N) and chronically hypoxic (CH) rats. Pulmonary vasodilation was observed by low-dose inhaled Beraprost in N rats, but not in CH rats. It was not until higher doses of Beraprost were given that pulmonary vasodilation was obtained in CH rats. When the agent was continuously administered by an intravascular route at the inhaled dose, it elicited no vasodilation in N rats. On the contrary, it elicited profound vasodilation in CH rats, although a concomitant systemic hypotension was observed. The PGI2 receptor mRNA expression was unchanged in the lungs of CH rats compared with that of N rats. We conclude that low doses of aerosolized Beraprost may reduce pulmonary vascular tone in rats without preexisting lung diseases. In contrast, when hypoxic pulmonary hypertension is present, the threshold of Beraprost inhalation was elevated to provoke pulmonary vasodilation.
Abe
Y
Y
Department of Chest Medicine, Chiba University School of Medicine, Japan. 9769abe@respi003.m.chiba-u.ac.jp
Tatsumi
K
K
Sugito
K
K
Ikeda
Y
Y
Kimura
H
H
Kuriyama
T
T
D000280:Administration, Inhalation; D000818:Animals; D002908:Chronic Disease; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D000860:Hypoxia / Q000503:physiopathology*; D007275:Injections, Intravenous; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000235:genetics
D012333:RNA, Messenger; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; C048081:beraprost; D011464:Epoprostenol