Nitric oxide release from normal and dysfunctional endothelium

The endothelium plays a critical role in maintaining vascular tone by releasing vasoconstrictor and vasodilator substances. Endothelium - derived nitric oxide (NO) is a vasodilator rapidly inactivated by superoxide (O-2(-)) found in significant quantities. The porphyrinic sensor (0.5-8 mu m diameter) and chemiluminescence methods were used to measure NO and O-2(-) respectively. Effects of hypertension, low density lipoprotein (LDL), and heart preservation on the:release of NO and O-2(-) were delineated. In the single endothelial cell (rat aorta) NO concentration was the highest in the cell membrane decreasing exponentially with distance from cell, and becoming undetectable beyond 50 mu m and 25 mu m for normotensive (WKY) and hypertensive (SHR) rats respectively. The endothelium of SHR released 40% less NO (300+/-25 nmol L-1) than that of normotensive rats (500+/-20 nmol L-1), due to the higher production of O-2(-) in SHR rats. An exponentially decreasing NO production (from 1.20+/-0.15 to 0.10+/-0.05 nmol L-1) and concomitant increase of O-2(-) generation (from 10+/-0.3 to 300+/-25 nmol L-1) were observed in left ventricle of stored (eight hours) rabbit heart. Native and oxidized low density lipoproteins (nLDL and oxLDL) inhibited NO generation and increased O-2(-) production. The local depletion of the L-arginine substrate may disarrange the nitric oxide synthase, leading to production of O-2(-) from oxygen.