Histamine elicits competing endothelium-dependent constriction and endothelium-independent dilation in vivo in mouse cerebral arterioles.
We used television microscopy and an image-splitting technique to monitor the changes in diameter produced by histamine applied locally to mouse pial arterioles in vivo. A high dose (50 micrograms/ml, 3 X 10(-4) M) of histamine constricted the arterioles, whereas lower doses (20 and 10 micrograms/ml) relaxed them. Constriction was blocked and dilation occurred when selective injury of the endothelium was produced by light from a helium-neon laser in the presence of intravascular Evans blue. From this we conclude that the constriction was endothelium-dependent and was caused by the release of an endothelium-derived constricting factor. Constriction was also blocked by each of two antagonists of the H1 histamine receptor and by pretreatment of the arterioles with indomethacin. H1 blockade unmasked a dilating action of 1 micrograms/ml histamine, a dose too low to affect the diameter of arterioles not treated with the H1 blocker. An H2 blocker interfered with the relaxation by low-dose (10 micrograms/ml, 6 X 10(-5) M) histamine. These data indicate that for mouse pial arterioles, histamine can interact with H1 receptors on the endothelium to release an endothelium-derived constricting factor that causes constriction of the underlying muscle while simultaneously interacting with H2 receptors in the muscle that mediate relaxation of the vessel.
Rosenblum
W I
WI
Department of Pathology (Neuropathology), Medical College of Virginia-Virginia Commonwealth University, Richmond 23298-0017.
Nelson
G H
GH
Weinbrecht
P
P
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005070:Evans Blue; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007834:Lasers; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010841:Pia Mater / Q000098:blood supply*; D014544:Uridine Triphosphate / Q000494:pharmacology; D014661:Vasoconstriction; D014664:Vasodilation
D006634:Histamine H1 Antagonists; D005070:Evans Blue; D002927:Cimetidine; D006632:Histamine; D014544:Uridine Triphosphate; D007213:Indomethacin