Casati C, Monopoli A, Forlani A, Bonizzoni E, Ongini E
Research Laboratories, Schering-Plough, Milan, Italy.
J Pharmacol Exp Ther. 1995 Nov;275(2):914-9.
Using the telemetry system in spontaneously hypertensive rats (SHR), we evaluated the hemodynamic effects of four adenosine analogs having different selectivity for A1 and A2a adenosine receptor subtypes. The selective A2a agonists, 2-hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA) and 2-[4-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoaden osi ne (CGS 21680), the selective A1 agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA) and the nonselective agonist, 5'-N-ethyl-carboxamidoadenosine (NECA), were administered i.p. to conscious spontaneously hypertensive rats. For comparison, the calcium channel blocker, felodipine, was included. CCPA and 2HE-NECA were tested also by the oral route. Systolic and diastolic blood pressure and heart rate were recorded every 5 min for 24 hr after drug administration. Data were analyzed using the curve fitting model recently elaborated. All compounds caused dose-dependent antihypertensive effects. The i.p. dose inducing a decrease of 50 mm Hg (ED50) was calculated for both systolic and diastolic blood pressure. As regards diastolic blood pressure, ED50 values were: CCPA, 0.019 (0.013-0.027) mg/kg, 2HE-NECA, 0.009 (0.002-0.03) mg/kg, CGS 21680, 0.155 (0.084-0.246) mg/kg, NECA, 0.008 (0.004-0.016) mg/kg and felodipine, 5.16 (4.18-7.18) mg/kg. At equiactive doses, the antihypertensive effects of adenosine agonists were shorter lasting [t1/2 for DBP were: CCPA, 54 (44-76) min, 2HE-NECA, 57 (46-71) min, CGS 21680, 45 (21-94) min, NECA, 61(38-97) min] than those of felodipine [t1/2 = 233 (182-274) min]. After oral administration (0.3, 1 and 3 mg/kg), hypotension induced by 2HE-NECA was longer lasting than that of CCPA. 2HE-NECA, CGS 21680 and felodipine caused tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)
利用遥测系统，我们在自发性高血压大鼠（SHR）中评估了四种对A1和A2a腺苷受体亚型具有不同选择性的腺苷类似物的血流动力学效应。将选择性A2a激动剂2-己炔基-5'-N-乙基羧酰胺腺苷（2HE-NECA）和2-[4-(2-羧乙基)-苯乙氨基]-5'-N-乙基羧酰胺腺苷（CGS 21680）、选择性A1激动剂2-氯-N6-环戊基腺苷（CCPA）以及非选择性激动剂5'-N-乙基羧酰胺腺苷（NECA）腹腔注射给清醒的自发性高血压大鼠。为作比较，还纳入了钙通道阻滞剂非洛地平。CCPA和2HE-NECA也通过口服途径进行了测试。给药后24小时内，每5分钟记录一次收缩压、舒张压和心率。使用最近精心构建的曲线拟合模型对数据进行分析。所有化合物均产生剂量依赖性降压作用。计算出收缩压和舒张压降低50 mmHg（ED50）的腹腔注射剂量。就舒张压而言，ED50值分别为：CCPA，0.019（0.013 - 0.027）mg/kg；2HE-NECA，0.009（0.002 - 0.03）mg/kg；CGS 21680，0.155（0.084 - 0.246）mg/kg；NECA，0.008（0.004 - 0.016）mg/kg；非洛地平，5.16（4.18 - 7.18）mg/kg。在等效活性剂量下，腺苷激动剂的降压作用持续时间较短[舒张压的t1/2分别为：CCPA，54（44 - 76）分钟；2HE-NECA，57（46 - 71）分钟；CGS 21680，45（21 - 94）分钟；NECA，61（38 - 97）分钟]，短于非洛地平[t1/2 = 233（182 - 274）分钟]。口服给药（0.3、1和3 mg/kg）后，2HE-NECA诱导的低血压持续时间长于CCPA。2HE-NECA、CGS 21680和非洛地平引起心动过速。（摘要截短至250字）
