SEPSIS ALTERS MYOCARDIAL AND PLASMA-CONCENTRATIONS OF ENDOTHELIN AND NITRIC-OXIDE IN RATS

Cardiovascular derangements during sepsis may arise from a mismatch be tween endothelin (ET) and nitric oxide (NO). We hypothesized that prog ression of chronic peritoneal sepsis would affect cardiac performance and would modulate the concentrations of NO and ET in the heart and pl asma. Male Sprague-Dawley rats (340-390 g) were catheterized and made septic with a cecal slurry (200 mg/kg; i.p.). Heart rate, mean arteria l pressure, and plasma ET and nitrite/nitrate (NOx) were determined at 0, 4, 8, 12, 24, and 48 h after induction of sepsis. Septic rats were found to have tachycardia at 48 h following induction of sepsis. Mean arterial pressure and pulse pressure were not altered in septic and n on-septic rats. In a separate series of experiments, the function of i solated hearts from septic and non-septic rats was assessed at preload pressures of 2, 5, and 10 mmHg, Sepsis produced a significant decreas e in rates of pressure development and relaxation (+/- dP/dt) at 24 an d 48 h as compared to the hearts of non-septic rats. In septic rats, p lasma concentrations of ET were significantly increased at t = 4, 8, 1 2 h as compared to basal values, and at 12 h as compared to non-septic rats, and returned to basal levels at 24 and 48 h. In contrast, circu lating NO levels did not become elevated until t = 8 h and remained el evated throughout the remaining times. In the left ventricle, the conc entration of ET was found to be significantly increased both in septic and non-septic rats at 4 and 8 h as compared to t = 0 h, In the left ventricles of non-septic rats, ET levels returned to baseline values a t 12 h, while in septic rats, the concentration of ET remained signifi cantly elevated until 12 h. In septic rats, left ventricular NO levels were found to be significantly increased at t = 12 h. It appeared tha t induction of sepsis contributed to an imbalance in the plasma concen tration of ET and NO 12 h after the induction of sepsis. However, a si milar imbalance was not observed in the left ventricle. It is conclude d from these observations that peritoneal sepsis in a chronic rat mode l produced a divergence of plasma NO and ET levels. This suggests a ho meostatic imbalance between vasoactive mediators, i.e. ET and NO, coul d contribute to the cardiovascular derangements that occur during seps is. (C) 1997 Academic Press Limited.