Endotoxin differentially impairs receptor-mediated relaxation in rat isolated pulmonary and thoracic aortic vessels.
OBJECTIVE
The purpose of this study was to determine the effect of endotoxin on vasorelaxation in the pulmonary and systemic circulations in response to the following agonists that require generation of cyclic adenosine monophosphate: (1) beta-adrenergic receptor stimulation with isoproterenol; (2) H2 receptor stimulation with dimaprit; and (3) adenylate cyclase stimulation with forskolin.


METHODS
Male Sprague-Dawley rats weighing 250 to 350 g were injected with endotoxin (20 mg/kg intraperitoneal) or saline. Six hours later, the cumulative dose response to beta-adrenergic receptor stimulation (isoproterenol), H2 receptor stimulation (dimaprit), and adenylate cyclase stimulation (forskolin) was determined in isolated rat pulmonary artery and thoracic aortic rings preconstricted with phenylephrine.


RESULTS
Endotoxin caused significant impairment of relaxation to isoproterenol in the pulmonary artery, but the response in the aorta was not different from the control response. In the pulmonary circulation, endotoxin converted the response to dimaprit from vasorelaxation to vasoconstriction. On the other hand, dimaprit resulted in vasorelaxation in the thoracic aorta after endotoxin; however, the response was impaired compared with the control response. Endotoxin did not affect the dose response to forskolin in either the pulmonary artery or the thoracic aorta.


CONCLUSIONS
From these data, we conclude that endotoxin causes regional specific changes in vascular reactivity. These changes in vascular reactivity result in preserved vasorelaxation in the systemic circulation and impairment of vasorelaxation in the pulmonary circulation in response to endotoxin.
McIntyre
R C
RC
Department of Surgery, University of Colorado Health Sciences Center and The Veterans Affairs Medical Center, Denver 80262, USA. robert.mcintyre@uchsc.edu
Pulido
E J
EJ
Sheridan
B
B
Meldrum
D R
DR
Bensard
D D
DD
Fullerton
D A
DA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D001775:Blood Circulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D017259:Dimaprit / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012485:Salmonella typhi; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D004731:Endotoxins; D017442:Histamine Agonists; D005576:Colforsin; D007545:Isoproterenol; D017259:Dimaprit