Author + information
- Yuchen Qian,
- Yu Wang,
- Xiaoqing Jiang,
- Yang Yang,
- Wangxiao Tan and
- Xiaoying Wang
Nitroglycerin (NTG) has been used for the treatment of cardiovascular diseases such as anginapectoris and heart failure, however, the NTG tolerance, which might compromise therapeutic efficacy, will be developed in prolonged prescription. The mechanism of the NTG tolerance mainly focused on superoxide anion (O2-) increasing, endothelial dysfunction and the activity of mitochondrial aldehyde dehydrogenase (ALDH-2) decreasing. Naoxintong capsule (NXT), a Chinese patent medicine extensively applied in clinic for stroke and coronary heart disease which approved by the China Food and Drug Administration. It's composed by 16 kinds of Chinese herbal medicines which mainly contain Astragali Radix, Salviae Miltiorrhizae Radix ET Rhizoma and Angelicae Sinensis Radix. Pharmacological research indicated that NXT could eliminate free radical of oxygen, protect mitochondria and endothelial cells. Therefore, it was considered that NXT might not only cure anginapectoris in combination with NTG, but also inhibit the NTG tolerance. We observed the effect of NXT on NTG tolerance in rats to provide theoretical basis for clinical practice.
Male Sprague-Dawley rats weighing 260-300g were divided into five groups randomly: (1) control group (CON), (2) nitroglycertin tolerance group (NTG tolerance), 50mg/kg daily, s.c.injections q.d.3 days, (3) - (5) groups given NTG with increasing dose of NXT (2.5, 5.0, 10.0mg/kg daily, s.c.injections q.d.3 days, NTG+NXT-L/M/H). Vevo 2100 Imaging System was employed to evaluate rats' cardiac function; the contents of malonaldehyde (MDA) and nitric oxide (NO) in blood were also detected.
The left ventricular (LV) ejection fraction (EF) by NTG tolerance was higher than that of CON, meanwhile the EF in NTG+NXT was significantly decreased than NTG tolerance. NTG+NXT-M could significantly improve the blood flow of LV outflow tract (LVOT) inhibition by NTG tolerance.The contents of MDA and NO showed a dramatically increased by NTG tolerance. NXT could decrease the excessive MDA and NO induced by NTG tolerance.
NXT could significantly inhibit the nitroglycerin tolerance by protecting cardiac function and reducing oxide stress. The corresponding clinical pharmacology might be related to expanding blood vessel and increasing blood flow.