Histamine inhibits conducted vasodilation through endothelium-derived NO production in arterioles of mouse skeletal muscle.
Conducted vasodilation along arterioles manifests the spread of hyperpolarization through gap junction channels along endothelium. Whereas histamine increases the permeability of capillary and venular endothelium, its effect on the integrity of arteriolar endothelium is unknown. We tested whether histamine could inhibit conducted vasodilation. In second-order arterioles (2A) supplying the cremaster muscle of C57BL6, PECAM-1-/-, and eNOS-/- mice (8-12 wk), neither resting (16+/-2 microm) nor maximal (38+/-2 microm) diameters were different. Acetylcholine (ACh) microiontophoresis (1 microA, 500 ms pulse) triggered vasodilation that was conducted >1400 microm along arterioles. Neither local (14+/-2 microm) nor conducted vasodilation (10+/-2 microm) was different among mice. Histamine (5 microM) had no effect on resting diameter or local vasodilation to ACh yet inhibited conduction by >50% in C57BL6 and PECAM-1-/- mice (P<0.05); this effect was abolished after blockade of NO synthase or of soluble guanylate cyclase. Washout of histamine restored conduction, though recovery was longer (P<0.05) in PECAM-1-/- mice vs. C57BL6 mice. Remarkably, conducted vasodilation in eNOS-/- mice was insensitive to histamine. These findings indicate that histamine inhibits cell-to-cell coupling through an NO-dependent mechanism and suggests a dynamic interaction among intercellular adhesion molecules and gap junction channels along arteriolar endothelium.
Payne
Geoffrey W
GW
The John B. Pierce Laboratory, Yale University School of Medicine,New Haven, Connecticut 06519, USA.
Madri
Joseph A
JA
Sessa
William C
WC
Segal
Steven S
SS
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D009569:Nitric Oxide; D006632:Histamine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D006162:Guanylate Cyclase; D000109:Acetylcholine