Sorrentino R, Pinto A
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
J Cardiovasc Pharmacol. 1997 May;29(5):599-604. doi: 10.1097/00005344-199705000-00006.
Nitric oxide produced by endothelial cells is a mediator involved in the regulation of vascular tone. Indeed, in vitro inhibition of basal nitric oxide release increase responses to vasoconstrictor agents, and in vivo, the parenteral or dietary administration of nitric oxide inhibitors produces an increase in blood pressure. However, the correlation of nitric oxide production and basal blood pressure in normotensive subjects is still unclear. In this study, we showed that administration, in urethane-anesthetized Wistar rat, of two inhibitors of nitric oxide synthase, such as NG-nitro-L-arginine methyl ester and methylguanidine, produced a significant increase in mean arterial blood pressure that was inversely related to basal mean arterial blood pressure at all doses tested. On the other hand, the increase in mean arterial blood pressure induced by infusion of angiotensin II did not correlate with basal mean arterial blood pressure. The pretreatment of rats with hexamethonium did not change the results observed in normal rats, ruling out an involvement of sympathetic nervous system. In conclusion, this study further confirms the presence of a tonic amount of nitric oxide, produced by endothelial cells in the bloodstream, which plays a key role in the regulation of basal blood pressure, and its reduction or inhibition may be the main cause of certain pathologic conditions characterized by high levels of blood pressure.
内皮细胞产生的一氧化氮是参与血管张力调节的一种介质。实际上，体外抑制基础一氧化氮释放会增强对血管收缩剂的反应，而在体内，注射或经饮食给予一氧化氮抑制剂会导致血压升高。然而，正常血压受试者中一氧化氮产生与基础血压之间的相关性仍不明确。在本研究中，我们表明，在氨基甲酸乙酯麻醉的Wistar大鼠中给予两种一氧化氮合酶抑制剂，如NG-硝基-L-精氨酸甲酯和甲基胍，会使平均动脉血压显著升高，且在所有测试剂量下，这种升高与基础平均动脉血压呈负相关。另一方面，输注血管紧张素II引起的平均动脉血压升高与基础平均动脉血压无关。用六甲铵预处理大鼠并未改变在正常大鼠中观察到的结果，排除了交感神经系统的参与。总之，本研究进一步证实了血流中内皮细胞产生的一定量的一氧化氮的存在，其在基础血压调节中起关键作用，其减少或抑制可能是以高血压为特征的某些病理状况的主要原因。
