Strawn W B, Gallagher P E, Tallant E A, Ganten D, Ferrario C M
The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina 27157-1032, USA.
J Cardiovasc Pharmacol. 1999 Mar;33(3):341-51. doi: 10.1097/00005344-199903000-00001.
This study investigated whether angiotensin II AT1-receptor blockade with losartan inhibits endothelium-monocyte interactions originating from long-term activation of the renin-angiotensin system in hypertensive transgenic rats [TGR(mRen2)27]. The number of circulating activated monocytes, monocytes adhered to thoracic aorta endothelium, and the extent of endothelial cell injury were compared in adult male transgenic (mRen2)27 and age-matched Hannover Sprague-Dawley (SD) rats after 12 days of continuous subcutaneous administration of saline (120 microl/24 h), losartan (10 mg/kg/24 h), or the vasodilator hydralazine (3 mg/kg/24 h). At the doses administered in this experiment, both losartan and hydralazine normalized mRen2 rat blood pressures equal to values in similarly treated SD rats. Compared with saline infusion, administration of either antihypertensive in mRen2 rats reduced (p<0.05) endothelial cell injury, but only losartan significantly (p<0.05) decreased the number of activated circulating and endothelium-adherent monocytes. Infusion of antihypertensives in SD rats had no effect on blood pressures, monocyte activity, or endothelial injury compared with saline administration. These findings suggest that the recruitment and infiltration of leukocytes into the subendothelium associated with renin-angiotensin system-induced hypertension is partly mediated by pressure-independent AT1-receptor pathways.
本研究调查了氯沙坦对血管紧张素II AT1受体的阻断是否能抑制高血压转基因大鼠[TGR(mRen2)27]中肾素-血管紧张素系统长期激活所引发的内皮细胞与单核细胞的相互作用。在成年雄性转基因(mRen2)27大鼠和年龄匹配的汉诺威-斯普拉格-道利(SD)大鼠中，连续皮下注射生理盐水(120微升/24小时)、氯沙坦(10毫克/千克/24小时)或血管扩张剂肼屈嗪(3毫克/千克/24小时)12天后，比较循环中活化单核细胞的数量、黏附于胸主动脉内皮的单核细胞数量以及内皮细胞损伤程度。在本实验所使用的剂量下，氯沙坦和肼屈嗪均使mRen2大鼠的血压恢复正常，与同样接受治疗的SD大鼠血压值相当。与输注生理盐水相比，给mRen2大鼠使用任何一种抗高血压药物均可减轻(p<0.05)内皮细胞损伤，但只有氯沙坦能显著(p<0.05)减少循环中活化的以及黏附于内皮的单核细胞数量。与输注生理盐水相比，给SD大鼠输注抗高血压药物对血压、单核细胞活性或内皮损伤均无影响。这些发现提示，与肾素-血管紧张素系统诱导的高血压相关的白细胞募集和浸润至内皮下的过程，部分是由不依赖压力的AT1受体途径介导的。
