Nitric oxide release from normal and dysfunctional endothelium

The endothelium plays a critical role in maintaining vascular tone by relea sing vasoconstrictor and vasodilator substances. Endothelium - derived nitr ic oxide (NO) is a vasodilator rapidly inactivated by superoxide (O-2(-)) f ound in significant quantities. The porphyrinic sensor (0.5-8 mu m diameter ) and chemiluminescence methods were used to measure NO and O-2(-) respecti vely. Effects of hypertension, low density lipoprotein (LDL), and heart pre servation on the:release of NO and O-2(-) were delineated. In the single en dothelial cell (rat aorta) NO concentration was the highest in the cell mem brane decreasing exponentially with distance from cell, and becoming undete ctable 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 pr oduction (from 1.20+/-0.15 to 0.10+/-0.05 nmol L-1) and concomitant increas e of O-2(-) generation (from 10+/-0.3 to 300+/-25 nmol L-1) were observed i n left ventricle of stored (eight hours) rabbit heart. Native and oxidized low density lipoproteins (nLDL and oxLDL) inhibited NO generation and incre ased 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.