Gardiner S M, March J E, Kemp P A, Bennett T
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Br J Pharmacol. 2001 Jun;133(3):445-53. doi: 10.1038/sj.bjp.0704100.
Regional haemodynamic responses to the cannabinoid agonist, WIN 55212-2 (5 - 250 microg kg(-1) i.v.) were assessed in conscious, normotensive, Hannover, Sprague-Dawley (HSD) rats, and in hypertensive, transgenic ((mRen-2)27) (abbreviated to TG) rats. In HSD rats, WIN 55212-2 caused pressor, and renal and mesenteric vasoconstrictor effects, with a hindquarters vasodilator effect occurring only at the highest dose. In TG rats, the effects of the cannabinoid agonist were qualitatively similar to those seen in HSD rats, except there was no hindquarters vasodilatation. In both strains of rat, in the presence of losartan, pentolinium and a vasopressin (V1-receptor) antagonist, the pressor and vasoconstrictor effects of WIN 55212-2 were abolished, but the hindquarters vasodilator response was enhanced (HSD rats) or was seen only in that circumstance (TG rats). Under these conditions, both strains of rat showed a modest fall in blood pressure, together with mesenteric vasodilatation. In additional experiments in normotensive SD rats from Charles River (CRSD), it was shown that, in the presence of the V1-receptor antagonist alone, or losartan alone, or the two antagonists together, the cardiovascular effects of WIN 55212-2 (50 or 150 microg kg(-1)) were not attenuated. Hence, the effects described above were likely due to pentolinium. There were no consistent differences between HSD and TG rats in their haemodynamic responses to methoxamine or noradrenaline, indicating the two strains were not likely to differ markedly in their responsiveness to any putative sympathetic activation induced by WIN 55212-2. Collectively, the results indicate that the predominant cardiovascular effects of WIN 55212-2 in conscious HSD and TG rats (i.e., pressor and vasoconstrictor actions) can be attributed largely to indirect, pentolinium-sensitive mechanisms, which appear to differ little in the normotensive and hypertensive state, at least in conscious animals. Under the conditions of our experiments, signs of cannabinoid-induced vasodilatation were modest.
在清醒、血压正常的汉诺威-斯普拉格-道利（HSD）大鼠以及高血压转基因（(mRen-2)27）（简称TG）大鼠中，评估了对大麻素激动剂WIN 55212-2（静脉注射5 - 250微克/千克）的局部血流动力学反应。在HSD大鼠中，WIN 55212-2引起升压作用以及肾和肠系膜血管收缩效应，仅在最高剂量时出现后肢血管舒张效应。在TG大鼠中，大麻素激动剂的效应在性质上与HSD大鼠中所见的相似，只是没有后肢血管舒张。在两种品系的大鼠中，在存在氯沙坦、潘托铵和血管加压素（V1受体）拮抗剂的情况下，WIN 55212-2的升压和血管收缩效应被消除，但后肢血管舒张反应增强（HSD大鼠）或仅在那种情况下出现（TG大鼠）。在这些条件下，两种品系的大鼠血压均出现适度下降，同时肠系膜血管舒张。在来自查尔斯河的正常血压SD大鼠（CRSD）的额外实验中表明，仅在存在V1受体拮抗剂、仅存在氯沙坦或两种拮抗剂同时存在的情况下，WIN 55212-2（50或150微克/千克）的心血管效应并未减弱。因此，上述效应可能归因于潘托铵。HSD和TG大鼠对甲氧明或去甲肾上腺素的血流动力学反应没有一致的差异，表明这两种品系对WIN 55212-2诱导的任何假定交感神经激活的反应性不太可能有明显差异。总体而言，结果表明WIN 55212-2在清醒HSD和TG大鼠中的主要心血管效应（即升压和血管收缩作用）在很大程度上可归因于间接的、对潘托铵敏感的机制，至少在清醒动物中，这些机制在正常血压和高血压状态下似乎差异不大。在我们的实验条件下，大麻素诱导的血管舒张迹象不明显。
