The role of nitric oxide in the cardiovascular system.
Nitric oxide (NO) exerts various pathophysiological effects on the cardiovascular system; inhibition of platelet aggregation or leukocyte adhesion on endothelium and vasorelaxation including lethal hypotension in endotoxic shock. In spite of these significant roles of NO, its direct action on individual cardiovascular cells remains unclarified. Therefore, we have investigated the function of NO on cells which constitute vascular wall and heart, and have found this new evidence. 1) ATP increased intracellular ([Ca2+]i) in vascular endothelial cells (ECs) and decreased [Ca2+]i of adjacently cocultured vascular smooth muscle cells (VSMCs), as detected by 2-D fura-2 image analysis. 2) The [Ca2+]i reduction in cocultured VSMCs with ECs by ATP was attenuated by pretreatment of several types of NO inhibitor, whereas the NO inhibitor potentiated the [Ca2+]i elevation in ECs, suggesting that NO affects VSMCs in a paracrine manner while ECs in an autocrine fashion. 3) Physiological concentration of lysophosphatidylcholine, which is an atherogenic constituent of oxidized LDL, but not native phosphatidylcholine, acted on ECs and VSMCs like a NO inhibitor, indicating that this material attenuates NO effect and disturbs vessel relaxation in the short term. 4) Highly efficient transfection of the ecNOS gene in rat heart showed a toxic effect on individual cardiomyocytes in vivo. In conclusion, NO may exert both beneficial and harmful effects on the cardiovascular system.
Shin
W S
WS
Second Department of Internal Medicine, University of Tokyo, Japan.
Kawaguchi
H
H
Sasaki
T
T
Wang
Y P
YP
Yang
W D
WD
Inukai
M
M
Toyo-Oka
T
T
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002319:Cardiovascular System / Q000187:drug effects*; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D002118:Calcium