Cilostazol therapy attenuates monocrotaline-induced pulmonary arterial hypertension in rat model.
BACKGROUND
Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance caused by a proliferation of vascular endothelial and smooth muscle cells, resulting in occlusion of the lumen of small pulmonary arteries. Cilostazol, with its antiproliferative effects on vascular endothelial and smooth muscle cells, may ameliorate monocrotaline (MCT)-induced PAH in rats.


RESULTS
Male Sprague - Dawley rats (n=10/each group) were randomized to receive MCT (75 mg/kg) only (group 1), MCT plus cilostazol (20 mg .kg(-1 ). day(-1)) (group 2) and saline injection only (group 3). Hemodynamic measurement on day 28 following MCT treatment indicated the development of significant PAH on MCT-treated groups (p<0.0001). Cilostazol was given to group 2 orally on days 28-90. By day 90 following MCT treatment, the right ventricular (RV) systolic blood pressure and RV hypertrophy were significantly higher in group 1 than in groups 2 and 3 (all values of p<0.01). Additionally, connexin43 and endothelial nitric oxide synthase gene expressions of lung and RV, and Bcl-2 protein expression of RV, were significantly lower in group 1 than in groups 2 and 3 (all values of p<0.01). Furthermore, the number of alveolar sac and small arterioles of the lung were significantly lower in group 1 than in groups 2 and 3 (all values of p<0.01).


CONCLUSIONS
Cilostazol therapy effectively attenuates of MCT-induced PAH.
Chang
Li-Teh
LT
Basic Science, Nursing Department, Meiho Institute of Technology, Pingtung.
Sun
Cheuk-Kwan
CK
Sheu
Jiunn-Jye
JJ
Chiang
Chiang-Hua
CH
Youssef
Ali A
AA
Lee
Fan-Yen
FY
Wu
Chiung-Jen
CJ
Yip
Hon-Kan
HK
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000077407:Cilostazol; D018031:Connexin 43 / Q000235:genetics; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D011650:Pulmonary Alveoli / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D018031:Connexin 43; D013777:Tetrazoles; D014665:Vasodilator Agents; D016686:Monocrotaline; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000077407:Cilostazol