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Effect of pharmacological agonists on contractile responses in aortic rings derived from endotoxaemic rats


, : Effect of pharmacological agonists on contractile responses in aortic rings derived from endotoxaemic rats. Journal of Veterinary Pharmacology & Therapeutics 19(5): 389-396

To investigate the vascular smooth muscle dysfunction of septic shock, in vitro isometric responses to phenylephrine (PE) and acetylcholine (ACh) were evaluated in aortic rings, with and without endothelium (+-E), removed from male Wistar rats 1.5, 3 and 6 h after intravenous (i.v.) administration of 5 mg/ kg lipopolysaccharide (LPS) or vehicle. A reduction in maximum contraction (+-E) and sensitivity (-E) to PE were identified at 6 but not at 1.5 or 3 h. Maximum relaxation to ACh (+E) was not affected by LPS treatment but sensitivity was increased at 1.5 and 3 h. Having identified 6 h as the time at which the most pronounced changes were observed, further studies at this interval found that maximum contraction to potassium chloride (+-E), prostaglandin F-2alpha (+E) and detomidine (-E) and relaxation to salbutamol (- E) were less in aortic rings from endotoxaemic rats. Sensitivity to KCl (+-E), PGF-2alpha (-E) and detomidine (-E) was also reduced. Relaxation to sodium nitroprusside and atrial natriuretic peptide was not changed. These results suggest that attenuated pressor responses to a variety of vasoactive agents may be expected in patients 6 h after systemic exposure to endotoxin and that this vasoplegia may influence the vascular side-effects of therapeutic agents.

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Accession: 002815839

PMID: 8905574

DOI: 10.1111/j.1365-2885.1996.tb00069.x

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