A model of chronic hypoxic pulmonary hypertension (HPH) was reconstructed in rats exposed to hypoxia with normal pressure for 14 d. Chronic HPH was prevented by giving Ligustrazine (LTZ) in an intraperitoneal dose of 80 mg ?kg-1 wt. twice daily. The mean pulmonary arterial pressure (mPAP), plasma and pulmonary small arterial cGMP level, and mRNA expression of nitric oxide synthase (NOS) gene in lung tissues were studied. The results showed that the mPAP was significantly higher, but plasma and pulmonary small arterial cGMP level as well as mRNA expression of NOS gene in lung tissues were markedly lower in chronic hypoxic rats than those in control animals. LTZcould reverse those changes of above indexes in hypoxic rats, but did not affect those indexes in normal rats. There was a strong negative correlation between cGMP level and mPAP. It is suggested that the lower mRNA expression of NOS gene in hypoxic rats may be one of pathogenetic mechanisms in chronic HPH, and LTZ can increase the mRNA exprssion of NOS gene and the production of nitric oxide in hypoxic rats, which may be an important mechanism in LTZ preventing chronic HPH.

In this study, whole cell patch clamp recording technique was employed to investigate the effect of Shenmai Injection (SMI) on L-type calcium current of diaphragmatic muscle in rats. The result showed that when the diaphragmatic muscle cell was held at -80 mV and depolarized to +60 mV, 10 microl/ml, 50 microl/ml and 100 microl/ml SMI enhanced the inner peak L-type calcium current from -(6.8 +/- 0.7) pA/pF (n=7) to -(7.3 +/- 0.8) pA/pF (P>0.05, n=7), -(8.6 +/- 1.0) pA/pF (P<0.05, n=7) and -(9.4 +/- 1.2) pA/pF (P<0.05, n=7), respectively, The rates of L-type calcium current were increased by (7.34 +/- 2.37)%, (25.72 +/- 5.94)%, and (38.16 +/- 7.33)%, respectively. However, it had no significant effect on maximal activation potential and reversal potential. Our results suggested that SMI could activate the calcium channel of the diaphragmatic fibers of the rats, increase the influx of Ca2+, and enhance the contractility of diaphragmatic muscles.
Calcium/metabolism ; Calcium Channels, L-Type/*drug effects ; Diaphragm/drug effects ; Diaphragm/*metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; Patch-Clamp Techniques ; Plant Extracts/*pharmacology ; Rats, Wistar

The effects of Shenmai injection (SMI) and aminophylline on apoptosis of small airway smooth muscle cells (SASMC) and the Fas/FasL expression in rats with papain-induced emphysema were investigated. Rat emphysema model was established by a single intratracheal instillation of papain. Apoptosis and Fas/FasL expression of SASMC were detected by immunohistochemistry SABC and TUNEL assay at day 1, 3, 5, 7, 15, 30 after modeling, and the effect of SMI and aminophylline on them were observed. The results indicated that the Fas/FasL expression positive rate in SASMC was 2.31 +/- 0.55/1.28 +/- 0.47 respectively. After a single intratracheal instillation of papain, the expression of Fas/FasL positive rate in the placebo group was increased in a time-dependent manner. SMI could inhibit the expression of Fas/FasL, but aminophylline couldn't. The positive rate of apoptosis in the control group was 0.87 +/- 0.32. After a single intratracheal instillation of papain, the SASMC apoptosis positive rate in the placebo group was increased in a time-dependent manner. The SASMC apoptosis rate in all groups was declined after treatment with SMI, but the effect of aminophylline was not obvious. It was demonstrated that in the pathogenesis of emphysema Fas/FasL played an important role in the regulation of SASMC apoptosis. SMI influenced the expression of Fas/FasL and declined SASMC apoptosis by inhibiting the releasing of inflammatory media and played an important role in the therapy of emphysema.
Aminophylline ; pharmacology ; Animals ; Bronchi ; metabolism ; pathology ; Bronchodilator Agents ; pharmacology ; Drug Combinations ; Drugs, Chinese Herbal ; Emphysema ; genetics ; pathology ; Fas Ligand Protein ; Female ; Gene Expression ; drug effects ; Male ; Membrane Glycoproteins ; biosynthesis ; genetics ; Myocytes, Smooth Muscle ; pathology ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; fas Receptor ; biosynthesis ; genetics

In this study, whole cell patch clamp recording technique was employed to investigate the effect of Shenmai Injection (SMI) on L-type calcium current of diaphragmatic muscle in rats. The result showed that when the diaphragmatic muscle cell was held at -80 mV and depolarized to +60 mV, 10 microl/ml, 50 microl/ml and 100 microl/ml SMI enhanced the inner peak L-type calcium current from -(6.8 +/- 0.7) pA/pF (n=7) to -(7.3 +/- 0.8) pA/pF (P>0.05, n=7), -(8.6 +/- 1.0) pA/pF (P<0.05, n=7) and -(9.4 +/- 1.2) pA/pF (P<0.05, n=7), respectively, The rates of L-type calcium current were increased by (7.34 +/- 2.37)%, (25.72 +/- 5.94)%, and (38.16 +/- 7.33)%, respectively. However, it had no significant effect on maximal activation potential and reversal potential. Our results suggested that SMI could activate the calcium channel of the diaphragmatic fibers of the rats, increase the influx of Ca2+, and enhance the contractility of diaphragmatic muscles.
Animals ; Calcium ; metabolism ; Calcium Channels, L-Type ; drug effects ; Diaphragm ; drug effects ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; Male ; Patch-Clamp Techniques ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar