Effects of atorvastatin and L-arginine treatments on electrical field stimulation-mediated relaxations in pulmonary arterial rings of monocrotaline-induced pulmonary hypertensive rats

J Cardiovasc Pharmacol. 2010 Nov;56(5):498-505. doi: 10.1097/FJC.0b013e3181f4838b.

Abstract

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.

MeSH terms

  • Animals
  • Arginine / pharmacology*
  • Atorvastatin
  • Electric Stimulation
  • Endothelium, Vascular / physiopathology
  • Heptanoic Acids / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hypertension, Pulmonary / chemically induced
  • Hypertension, Pulmonary / metabolism
  • Hypertension, Pulmonary / physiopathology*
  • In Vitro Techniques
  • Male
  • Monocrotaline
  • Nitric Oxide / physiology
  • Nitric Oxide Synthase Type III / metabolism
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / physiopathology
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Vasodilation / drug effects*

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Nitric Oxide
  • Monocrotaline
  • Arginine
  • Atorvastatin
  • Nitric Oxide Synthase Type III