Sepsis alters myocardial and plasma concentrations of endothelin and nitric oxide in rats

Abstract

Cardiovascular derangements during sepsis may arise from a mismatch between endothelin (ET) and nitric oxide (NO). We hypothesized that progression of chronic peritoneal sepsis would affect cardiac performance and would modulate the concentrations of NO and ET in the heart and plasma. Male Sprague-Dawley rats (340-390 g) were catheterized and made septic with a cecal slurry (200 mg/kg: i.p.). Heart rate, mean arterial 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 non-septic rats. In a separate series of experiments, the function of isolated hearts from septic and non-septic rats was assessed at preload pressures of 2, 5, and 10 mmHg. Sepsis produced a significant decrease in rates of pressure development and relaxation (+/-dP/dt) at 24 and 48 h as compared to the hearts of non-septic rats. In septic rats, plasma concentrations of ET were significantly increased at t = 4, 8, 12 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, circulating NO levels did not become elevated until t = 8 h and remained elevated throughout the remaining times. In the left ventricle, the concentration 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 at 12 h, while in septic rats, the concentration of ET remained significantly elevated until 12 h. In septic rats, left ventricular NO levels were found to be significantly increased at t = 12 h. It appeared that induction of sepsis contributed to an imbalance in the plasma concentration of ET and NO 12 h after the induction of sepsis. However, a similar imbalance was not observed in the left ventricle. It is concluded from these observations that peritoneal sepsis in a chronic rat model produced a divergence of plasma NO and ET levels. This suggests a homeostatic imbalance between vasoactive mediators, i.e. ET and NO, could contribute to the cardiovascular derangements that occur during sepsis.