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

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.