SEPSIS DECREASES PHENYLEPHRINE-INDUCED 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 endotoxemi a. The purpose of the present investigation was to determine mechanism s responsible for the abnormal contractility in sepsis using the rat c ecal ligation and perforation (CLP) model. 24 h after CLP or sham surg ery, rats were anesthetized with halothane and a segment of the thorac ic aorta removed. Aortic rings measuring 1.6-2.0 mm in length were mou nted in a water bath and stretched to optimal diameter. Aortic rings f rom control rats demonstrated a 57% increase in maximum contraction to phenylephrine and a 68% increase to KCI compared to aortic rings from rats with sepsis (p < .01). There was no difference in the concentrat ions of phenylephrine or KCI which elicited a half-maximal contraction (EC(50)) in control versus septic aortic rings. Removal of the endoth elium increased the sensitivity of aortas to both phenylephrine and KC I in septic and control aortic rings but did not reverse the defects i n contraction in sepsis. Treatment of the aortic rings with N gamma-ni tro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibito r, 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 occu rred with phenylephrine were slower, i.e.,.07 +/- .10 vs. .17 +/- .02 Hz, for septic and control rings, respectively (p < .05), and had a gr eater amplitude .65 +/- .01 vs. .41 +/- .09 mN/mm, for septic and cont rol rings, respectively (p < .05). This is consistent with an effect o f sepsis on calcium uptake and/or release from intracellular pools. We conclude that the abnormality in vascular contraction to phenylephrin e in sepsis is not due to defects in a:adrenergic receptors or excessi ve nitric oxide but may be related to effects of sepsis on intracellul ar calcium storage organelles.