【摘要】 目的和方法 :采用HO活性抑制剂诱导大鼠高血压模型 ,观察血压变化、主动脉HO和NOS活性、CO和NO产生释放 ,并测定血浆和主动脉平滑肌组织中cGMP含量 ,以探讨内源性NO和CO在高血压发生机制中的作用及其相互关系。结果 :大鼠应用HO抑制剂ZnDPBG腹腔注射 2周后 ,继续饲养到第 4周出现持续而稳定的高血压 ,同时总NOS(tNOS)和诱导型NOS(iNOS)的活性分别增加 45 .4%和 73 .3 % (均为P <0 .0 1) ,血管孵育液中 [NO2 -]也明显高于正常。同时加入ZnDPBG和NOS底物左旋精氨酸 (L arginine ,L Arg) ,血压虽然仍高于正常 ,但比单纯ZnDPBG处理的大鼠血压要明显降低 ,此时iNOS活性和 [NO2 -]产生的增加更明显。血浆和主动脉平滑肌组织中cGMP含量的改变与iNOS活性变化相一致。结论 :在慢性给予HO抑制剂所诱导的高血压发生过程中NOS/NO系统出现上调 ;应用NOS底物使NO产生增加时 ,能部分性逆转血压的增高 ,这一效应主要通过cGMP途径所介导。实验提示 ,体内NOS/NO系统与HO/CO系统存在相互作用和相互代偿调节 ,两者的代偿失调或代偿不全可能是高血压发生发展的重要机制之一更多还原

【Abstract】 Aim and Methods: This study was to investigate the relationships between endogenous carbon monoxide (CO) and nitric oxide (NO) in regulating the pathogenesis of hypertension induced by heme oxygenase (HO) inhibition in rats. The blood pressure (BP) of rats was measured and the HO activity, HbCO formation, NO synthase (NOS) activity, [NO 2-] and cGMP content in plasma or tissues were examined. Results: BP of animals at the 4th week was significantly elevated after treatment of HO inhibitor, zinc deuteroporphyrin 2,4bisglycol (ZnDPBG), while the [NO 2-], iNOS and tNOS activity derived from the aortic smooth muscle tissues were significantly increased by 53.3% (P<0.05),73.3% and 45.4%(P<0.01),respectively. Interestedly, the BP in ZnDPBG and Larginine (LArg, NOS substrate)treated group was significantly decreased compared with that in ZnDPBGtreated group solely, although it was still higher than that of control group. Changes of cGMP in plasma or tissues were similar with that of iNOS activity. Our data revealed that NOS/NO system was upregulated during the hypertension formation. NOS substrate could partly recover the BP level via increasing NO production. Conclusion: NOS/NO and HO/CO systems might act each other during hypertension formation, and the imbalance between NOS/NO and HO/CO pathways be one of the important mechanisms of pathogenesis of hypertension.更多还原