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

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Abstract
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 F2 alpha (+E) and detomidine (-E) and relaxation to salbutamol (-E) were less in aortic rings from endotoxaemic rats. Sensitivity to KCl (+/-E), PGF2 alpha (-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.