The endothelium-dependent effects of thimerosal on mouse pial arterioles in vivo: evidence for control of microvascular events by EDRF as well as prostaglandins.
Thimerosal causes synthesis and/or release of both endothelium-derived relaxing factor (EDRF) and prostaglandins from conductance vessels in vitro. We tested its effects and mechanism of action on mouse pial arterioles in vivo using intravital microscopic techniques. Topical thimerosal dilated pial arterioles. This effect was eliminated by endothelial injury produced by a laser/Evans blue technique. Dilation was also eliminated by topical L-NMMA, a reported inhibitor of EDRF synthesis. Topical thimerosal also reduced the incidence of platelet adhesion/aggregation ("capture") at a site of minimal endothelial damage. This effect was eliminated by L-NMMA pretreatment. The ability of thimerosal to dilate arterioles was eliminated not only by treatments thought to eliminate synthesis/release of EDRF, but also by cyclooxygenase inhibitors. However, inhibition of platelet adhesion/aggregation was not affected by cyclooxygenase inhibition. Thimerosal significantly increased production of prostaglandin E2 recovered from a closed cranial window. We conclude that the dilating effects of thimerosal on diameter require two endothelium-derived agents: EDRF and one or more prostaglandins acting in concert. However, the inhibiting effect of thimerosal on local platelet adhesion/aggregation appears to be caused only by an increase in EDRF at the injured site.
Rosenblum
W I
WI
Department of Pathology (Neuropathology), Medical College of Virginia, Richmond 23298-0017.
Nishimura
H
H
Ellis
E F
EF
Nelson
G H
GH
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply*; D013849:Thimerosal / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine
D013849:Thimerosal; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D001120:Arginine; D015232:Dinoprostone