Van de Voorde J, Claeys M, Leusen I
Laboratory of Normal and Pathological Physiology, University of Gent, Belgium.
J Cardiovasc Pharmacol. 1989;14 Suppl 11:S55-61.
The effects of SIN-1 were studied on isolated aortic rings and perfused hindquarters of the rat and were compared with the effects of nitroglycerin and endothelium-derived relaxing factor (EDRF) released by acetylcholine or histamine (aorta) and carbachol (hindquarters). SIN-1 relaxes rat aortic rings in a dose-dependent and endothelium-independent way. Aortic rings made tolerant to nitroglycerin in vitro show cross-tolerance to isosorbide dinitrate but no cross-tolerance to EDRF, sodium nitroprusside, or SIN-1. Aortic rings made tolerant to nitroglycerin by in vivo treatment show an important cross-tolerance to isosorbide dinitrate, a small degree of tolerance to sodium nitroprusside, but no significant tolerance to SIN-1 or EDRF. Also, in the nitroglycerin-tolerant hindquarter vasculature, no cross-tolerance is found to EDRF or SIN-1. In the aorta of renal hypertensive rats, in which the relaxation to EDRF-dependent dilators is impaired, no depression of the maximal response to SIN-1 occurs.
研究了SIN-1对大鼠离体主动脉环和灌注后肢的作用，并与硝酸甘油以及乙酰胆碱或组胺（主动脉）和卡巴胆碱（后肢）释放的内皮衍生舒张因子（EDRF）的作用进行了比较。SIN-1以剂量依赖性和不依赖内皮的方式使大鼠主动脉环舒张。体外对硝酸甘油产生耐受性的主动脉环对异山梨醇二硝酸酯表现出交叉耐受性，但对EDRF、硝普钠或SIN-1没有交叉耐受性。通过体内处理对硝酸甘油产生耐受性的主动脉环对异山梨醇二硝酸酯表现出重要的交叉耐受性，对硝普钠有轻度耐受性，但对SIN-1或EDRF没有显著耐受性。此外，在对硝酸甘油耐受的后肢血管系统中，未发现对EDRF或SIN-1的交叉耐受性。在肾性高血压大鼠的主动脉中，对依赖EDRF的舒张剂的舒张作用受损，但对SIN-1的最大反应未出现抑制。
