title: Atracurium induced vasodilatation is not mediated by histamine in the isolated femoral artery of the rabbit.
abstract: Atracurium causes a decrease in systemic vascular resistance (SVR) and mean arterial blood pressure (MAP) which has been ascribed to histamine release. However, histamine receptor blockade does not prevent these decreases completely. The hypotensive side effects of atracurium may not only be caused by histamine. In this study we examined the vasoactive effects of atracurium with and without histamine receptor blockade in an isolated femoral artery preparation of the rabbit. We also investigated whether vasodilatation caused by atracurium depends on the presence of endothelial cells. Tyrode perfused, rabbit femoral arteries were constricted with noradrenaline (NA) to +/- 70% of their passive diameter. Endothelial function was checked with acetylcholine (ACh). The vessels were divided into two groups. In both groups the responses to histamine (1.0-10(-6)M) and atracurium (3.2-10(-5)M) were determined. In group one (n = 5), the histamine and atracurium responses were repeated during histamine receptor blockade. In group two (n = 5), the diameter responses to histamine and atracurium before and after endothelium removal were compared. Also, some vessel segments (n = 5) were histologically prepared and examined for mast cells. The vasodilatory responses to atracurium both with and without histamine receptor blockade were the same. Removal of endothelium caused an increase in the histamine response, while the dilating response to atracurium remained constant. We conclude that in the isolated femoral artery of the rabbit, atracurium induces, vasodilatation that is not mediated by histamine release and cannot be prevented with histamine receptor blockade. The mechanism of atracurium induced dilation is independent of the endothelium and is located in the smooth muscle cell.
authors.affiliation: Laboratory for Physiiology, Free University, Amsterdam, The Netherlands.
authors.forename: D M
authors.initials: DM
authors.lastname: de Jong
authors.forename: N
authors.initials: N
authors.lastname: Hoogerwerf
authors.forename: G J
authors.initials: GJ
authors.lastname: Scheffer
authors.forename: J J
authors.initials: JJ
authors.lastname: de Lange
authors.forename: H H
authors.initials: HH
authors.lastname: Ros
authors.forename: P
authors.initials: P
authors.lastname: Sipkema
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001279:Atracurium / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D005263:Femoral Artery / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology* / Q000502:physiology; D006633:Histamine Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D011968:Receptors, Histamine / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D006633:Histamine Antagonists; D003473:Neuromuscular Nondepolarizing Agents; D011968:Receptors, Histamine; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D001279:Atracurium; D006632:Histamine; D000109:Acetylcholine; D009638:Norepinephrine