Influence of histaminergic receptors on denervated canine gracilis muscle vascular tone during endotoxemia.
The purpose of this study was to determine if endogenously released histamine and its non-neural interaction with the H1- and H2-histaminergic receptors in the peripheral vasculature can account for the decompensatory loss of peripheral vascular tone associated with the hypotension occurring during endotoxemia. A denervated in situ constant flow double canine gracilis muscle preparation that permitted one muscle to serve as a control (GMc) for the contralateral experimental muscle (GMe) was used. Endotoxemia was induced by intravenous infusion of 2 mg.kg-1.30 min-1 endotoxin. The specific H1 and H2 antagonists diphen-hydramine and cimetidine were infused either together or separately in both high and low dosages into the GMe. Blockades were validated by intra-arterial injection of histamine or the specific agonists betahistine for H1 and dimaprit for H2 receptors. The results suggest that the high-dose diphenhydramine produced a nonspecific dilation not seen with the lower dose. Because both the blocked and unblocked vascular beds exhibited the same degree of vasodilation after endotoxin, these studies do not support the hypothesis that endogenously released histamine is responsible for the loss of vascular tone. These studies do verify, however, that a nonneurally mediated loss of skeletal muscle vascular tone is an important factor to consider in the overall cardiovascular hypotension occurring during endotoxin shock.
Bond
R F
RF
Department of Physiology, University of South Carolina School of Medicine, Columbia 29208.
Vildibill
H D
HD
Krech
L H
LH
Hershey
J C
JC
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology*; D004155:Diphenhydramine / Q000494:pharmacology*; D004285:Dogs; D004731:Endotoxins / Q000633:toxicity; D004926:Escherichia coli; D006632:Histamine / Q000494:pharmacology*; D009121:Muscle Denervation; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009132:Muscles / Q000098:blood supply* / Q000294:innervation / Q000503:physiopathology; D011311:Pressoreceptors / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012772:Shock, Septic / Q000503:physiopathology*
D004731:Endotoxins; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine; D000241:Adenosine