Protective effect of beraprost sodium, a stable prostacyclin analogue, in development of monocrotaline-induced pulmonary hypertension.
Experimental pulmonary hypertension (PH) was induced by a single injection of monocrotaline (MCT), a pyrrolizidine alkaloid extracted from Crotalaria spectabilis. The effect of beraprost sodium, a stable prostacyclin analogue, on the development of MCT-induced PH in rats was studied. Chronic administration of beraprost sodium at a dose of 30 micrograms/kg/day initiated on the same day as MCT injection decreased the degree of PH determined by weight ratio of right ventricular free wall to that of left ventricle plus septum depending on the duration of administration. Although the injection of prostaglandin E1 (PGE1) at a dose of 200 micrograms/kg/day initiated 1 week after MCT injection did not decrease the degree of PH significantly, beraprost sodium administration at doses of 30 and 100 micrograms/kg/day decreased the degree of PH significantly. The cytoprotective effect of beraprost sodium against endothelial cell (EC) damage is believed to be involved in inhibiting development of PH in MCT-injected rats. The amounts of cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) produced by alveolar macrophages decreased in accordance with the inhibiting effect of beraprost sodium on development of PH, indicating that beraprost sodium inhibited the development of PH in MCT-injected rats not only through its effect of vasodilation and anti-platelet aggregation in pulmonary circulation but also through its antiinflammatory effects.
Miyata
M
M
Department of Internal Medicine II, Fukushima Medical College, Japan.
Ueno
Y
Y
Sekine
H
H
Ito
O
O
Sakuma
F
F
Koike
H
H
Nishio
S
S
Nishimaki
T
T
Kasukawa
R
R
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000145:classification / Q000517:prevention & control*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D016686:Monocrotaline / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011042:Poisons; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; D011042:Poisons; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; C014114:monocrotaline pyrrole; C048081:beraprost; D016686:Monocrotaline; D011464:Epoprostenol; D000527:Alprostadil