Total ginsenosides inhibit the right ventricular hypertrophy induced by monocrotaline in rats.
Ginsenosides have been reported to release nitric oxide (NO) and decrease intracellular free Ca(2+) in cardiovascular system, which play important roles in antihypertrophic effect. This study investigated the potential inhibitory effect of total ginsenosides (TG) on right ventricular hypertrophy induced by monocrotaline (MCT, 60 mg/kg/d) and examined the possible antihypertrophic mechanism in male Sprague Dawley rats. MCT-intoxicated animals were treated with TG (20, 40, 60 mg/kg/d) for 18 d. TG treatment ameliorated MCT-induced elevations in right ventricular peak systolic pressure, right ventricular hypertrophy and the expression of atrial natriuretic peptide; N(G)-nitro-L-arginine-methyl ester (L-NAME), an NO synthase (NOS) inhibitor, had no influence on these inhibitory effects of TG 40 mg/kg/d, and TG at this dose had no any effect on the eNOS mRNA expression, suggesting the limited rule of NO in TG's effects. To further examine the mechanisms of the protection, the expression of calcineurin and its catalytic subunit CnA, as well as extracellular signal-regulated kinase-1 (ERK-1) and mitogen-activated protein kinase (MAPK) Phosphatase-1 (MKP-1) was examined. TG treatment significantly suppressed MCT-induced elevations of these signaling pathways in a dose-dependent manner. In summary, TG is effective in protecting against MCT-induced right ventricle hypertrophy, possibly through lowering pulmonary hypertension. Multiple molecular mechanisms appeared to be involved in this protection, such as the suppression of MCT-activated calcineurin and ERK signaling pathways.
Qin
Na
N
Department of Pharmacology, Zunyi Medical College, Zunyi, China.
Gong
Qi-Hai
QH
Wei
Li-Wei
LW
Wu
Qin
Q
Huang
Xie-Nan
XN
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000473:pathology / Q000517:prevention & control; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008168:Lung / Q000473:pathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016686:Monocrotaline / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005894:Panax / Q000737:chemistry; D011042:Poisons / Q000633:toxicity*; D011652:Pulmonary Circulation / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
D004791:Enzyme Inhibitors; D036145:Ginsenosides; D011042:Poisons; D009569:Nitric Oxide; D012313:RNA; D016686:Monocrotaline; D019001:Nitric Oxide Synthase; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D019331:NG-Nitroarginine Methyl Ester