NG-monomethyl-L-arginine increases platelet deposition on damaged endothelium in vivo. A scanning electron microscopic study.
There is increasing evidence that nitric oxide (NO) synthetized in vascular endothelium and in platelets by NO synthase influences vascular tone, down regulates platelet function and platelet-vessel wall interaction both in vitro and in vivo. We investigated the effect of a NO synthase inhibitor, NG-mono-methyl-L-arginine (L-NMMA, 100 mg/kg iv) on platelet-endothelial cell interaction in rabbit arteries ex vivo using scanning electron microscope (SEM). The effect of L-NMMA was examined on intact endothelium and on that damaged by arterial constriction. The infusion of L-NMMA increased systemic blood pressure and decreased carotid blood flow, however, it did not change the appearance of an intact endothelium and did not result in platelet activation on intact endothelial cells. In contrast, SEM of endothelial areas damaged by constriction showed extensive platelet adhesion and aggregation on subendothelium. These morphological changes were not detected in control animals with intact or damaged by arterial constriction endothelium. These results show that under physiological conditions, the inhibition of NO synthase alone does not result in platelet activation in vivo. However, when combined with endothelial injury it may lead to platelet activation and thrombosis.
Herbaczyńska-Cedro
K
K
Cardiovascular Laboratory, Polish Academy of Sciences, Warsaw.
Lembowicz
K
K
Pytel
B
B
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D019001:Nitric Oxide Synthase; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D019323:omega-N-Methylarginine
D010975:Platelet Aggregation Inhibitors; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases