Effects of atorvastatin and L-arginine treatments on electrical field stimulation-mediated relaxations in pulmonary arterial rings of monocrotaline-induced pulmonary hypertensive rats.
This study aimed to examine the effect of monocrotaline (MCT)-induced pulmonary hypertension on electrical field stimulation (EFS)-mediated relaxation in rings of rat main pulmonary artery and to see whether treatment with atorvastatin or L-arginine would prevent the action of MCT. Rats were killed 21 days after MCT injection (60 mg/kg), and the main pulmonary arteries were isolated. EFS (40 V, 0.2 milliseconds, 5 seconds, 10 Hz)-induced relaxations in vessels precontracted with phenylephrine (10(-6) to 3 × 10(-6) M) were abolished in MCT-injected group compared with control group. Treatment of MCT group with atorvastatin (10 mg/kg, orally) completely, whereas treatment with L-arginine (500 mg/kg, intraperitoneally) partially but significantly prevented the inhibition. Similarly, acetylcholine (10(-9) to 3 × 10(-5) M)-evoked relaxations that were markedly inhibited in MCT-group were also protected from inhibition after pretreatment with atorvastatin or L-arginine. Responses to endothelium-independent relaxants sodium nitroprusside (10(-9) to 10(-5) M), pinacidil (10(-10) to 10(-4) M), and papaverine (10(-8) to 10(-4) M) were unaltered in MCT-induced pulmonary hypertensive rats. The present findings suggest that MCT-induced pulmonary hypertension inhibits the EFS-mediated relaxation through suppression of endothelial NO production. Reversal of this inhibition by atorvastatin treatment presumably results from stimulation of endothelial nitric oxide synthase expression. Relatively weak protection elicited by L-arginine might be secondary to impaired endothelial nitric oxide synthase activity caused by MCT-induced pulmonary hypertension.
Ozturk
Elif Inci
EI
Department of Pharmacology, Faculty of Pharmacy, University of Hacettepe, Sihhiye, Ankara, Turkey.
Uma
Serdar
S
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D000069059:Atorvastatin; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000503:physiopathology; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D016686:Monocrotaline; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D009569:Nitric Oxide; D016686:Monocrotaline; D001120:Arginine; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III