Tsui Debbie Y Y, Gambino Agatha, Wanstall Janet C
School of Biomedical Sciences, Department of Physiology and Pharmacology, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
J Pharm Pharmacol. 2003 Aug;55(8):1121-5. doi: 10.1211/0022357021369.
The effects of S-nitrosocaptopril (SNOcap), administered either intravenously or by oral gavage, on pulmonary artery pressure (PAP) were examined in anaesthetised normotensive rats and rats with hypoxic pulmonary hypertension (10% oxygen for 1 week). Mean PAP (MPAP) values in hypoxic and normoxic rats were (mmHg) 26 +/- 1.7 and 15 +/- 1.1, respectively. When given intravenously, 1 mg kg(-1) SNOcap reduced MPAP by 28 and 32% in hypoxic and normoxic rats, respectively. The effects of 2 mg kg(-1) were no greater than those of 1 mg kg(-1). Pulmonary vasodepressor responses reached equilibrium in 1.7 +/- 0.18 min following intravenous administration. When given orally 30 min before the measurement of PAP, 30 mg kg(-1), but not 10 mg kg(-1), significantly reduced MPAP in hypoxic rats to 17 +/- 1.5 mmHg. These in-vivo data are consistent with previous in-vitro data showing that SNOcap has direct pulmonary vasorelaxant properties in both large and small pulmonary arteries and also show that SNOcap causes pulmonary vasodepression in the setting of pulmonary hypertension. Since SNOcap also inhibits pulmonary vascular angiotensin converting enzyme (ACE) in pulmonary blood vessels (previous study), it would be an interesting drug with which to assess the benefits of direct pulmonary vasodilatation combined with ACE inhibition (which attenuates pulmonary vascular remodelling) in a long-term study in pulmonary hypertension.
在麻醉的正常血压大鼠和低氧性肺动脉高压大鼠（10%氧气，持续1周）中，研究了静脉注射或灌胃给予S-亚硝基卡托普利（SNOcap）对肺动脉压（PAP）的影响。低氧和正常氧大鼠的平均肺动脉压（MPAP）值分别为（mmHg）26±1.7和15±1.1。静脉给予1mg/kg SNOcap时，低氧和正常氧大鼠的MPAP分别降低28%和32%。2mg/kg的效果不大于1mg/kg。静脉给药后1.7±0.18分钟，肺血管舒张反应达到平衡。在测量PAP前30分钟口服给药时，30mg/kg而非10mg/kg可使低氧大鼠的MPAP显著降低至17±1.5mmHg。这些体内数据与之前的体外数据一致，表明SNOcap在大、小肺动脉中均具有直接的肺血管舒张特性，也表明SNOcap在肺动脉高压情况下可导致肺血管舒张。由于SNOcap还抑制肺血管中的肺血管紧张素转换酶（ACE）（先前研究），在一项关于肺动脉高压的长期研究中，它将是一种用于评估直接肺血管扩张与ACE抑制（可减轻肺血管重塑）联合作用益处的有趣药物。
