Endothelium-dependent L-Arg- and L-NMMA-sensitive mechanisms regulate tone of brain microvessels.
Pial arterioles on the surface of the mouse brain were observed via television microscopy and measured with an image-splitting technique. The vessels were dilated by L-arginine (L-Arg) in concentrations as low as 10(-5) M and were constricted in dose-dependent manner by NG-monomethyl-L-arginine (L-NMMA). Both the dilation and the constriction were abolished by endothelial damage. This damage was produced over a short segment of endothelium by a well-established technique that involves exposing the endothelium to a helium-neon laser in the presence of intravascular Evans blue dye. In arterioles that were responsive to 10(-5) M L-Arg, five other L-amino acids, also at 10(-5) M, failed to have any effect. The data provide direct evidence for the endothelium-dependent nature of the responses to L-Arg and L-NMMA in vivo in a defined segment of the cerebral vasculature. L-NMMA inhibited dilation by either L-Arg or acetylcholine. The data are consistent with data from in vitro studies and from studies demonstrating that L-NMMA acutely raises blood pressure. From all these earlier studies it has been hypothesized that there is a continuously acting, endothelium-dependent, L-Arg-dependent, and L-NMMA-inhibitable mechanism tending to relax blood vessels. The mediator of this mechanism is thought to be the endothelium-dependent relaxing factor for acetylcholine. Our data suggest that this mechanism is acting in the resistance vessels of the brain in vivo.
Rosenblum
W I
WI
Department of Pathology (Neuropathology), Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0017.
Nishimura
H
H
Nelson
G H
GH
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008833:Microcirculation / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D014664:Vasodilation; D019323:omega-N-Methylarginine
D000596:Amino Acids; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D001120:Arginine; D000109:Acetylcholine