Sepsis decreases phenylephrine- and KCl-induced aortic ring contraction and decreases the frequency of oscillations in active wall tension.
Impaired vascular contractility is a hallmark of sepsis and endotoxemia. The purpose of the present investigation was to determine mechanisms responsible for the abnormal contractility in sepsis using the rat cecal ligation and perforation (CLP) model. 24 h after CLP or sham surgery, rats were anesthetized with halothane and a segment of the thoracic aorta removed. Aortic rings measuring 1.6-2.0 mm in length were mounted in a water bath and stretched to optimal diameter. Aortic rings from control rats demonstrated a 57% increase in maximum contraction to phenylephrine and a 68% increase to KCl compared to aortic rings from rats with sepsis (p < .01). There was no difference in the concentrations of phenylephrine or KCl which elicited a half-maximal contraction (EC50) in control versus septic aortic rings. Removal of the endothelium increased the sensitivity of aortas to both phenylephrine and KCl in septic and control aortic rings but did not reverse the defects in contraction in sepsis. Treatment of the aortic rings with N gamma-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, increased contraction in aortic rings from both septic and control rats but also failed to correct the contractile defect in sepsis. The frequency and amplitude of the oscillations in wall tension which occurred with phenylephrine were slower, i.e., .07 +/- .10 vs. .17 +/- .02 Hz, for septic and control rings, respectively (p < .05), and had a greater amplitude .65 +/- .01 vs. .41 +/- .09 mN/mm, for septic and control rings, respectively (p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Heesen
B J
BJ
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
Hotchkiss
R S
RS
Karl
I E
IE
D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D002432:Cecum; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D005260:Female; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009991:Oscillometry; D010656:Phenylephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018805:Sepsis / Q000503:physiopathology*; D013997:Time Factors
D010656:Phenylephrine; D011189:Potassium Chloride