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 (O2-) found in significant quantities. The porphyrinic sensor (0.5-8 microm diameter) and chemiluminescence methods were used to measure NO and (O2-) respectively. Effects of hypertension, low density lipoprotein (LDL), and heart preservation on the release of NO and O2- 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 microm and 25 microm 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 O2- in SHR rats. An exponentially decreasing NO production (from 1.20 +/- 0.15 to 0.16 +/- 0.05 micromol (L-1)) and concomitant increase of O2- 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 O2- production. The local depletion of the L-arginine substrate may disarrange the nitric oxide synthase, leading to production of O2- from oxygen.
Brovkovych
V
V
Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA.
Dobrucki
L W
LW
Brovkovych
S
S
Dobrucki
I
I
Do Nascimento
C A
CA
Burewicz
A
A
Malinski
T
T
D000818:Animals; D002478:Cells, Cultured; D008078:Cholesterol, LDL / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009926:Organ Preservation / Q000009:adverse effects; D011166:Porphyrins / Q000032:analysis; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
D008078:Cholesterol, LDL; D011166:Porphyrins; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase