Alterations of coronary perfusion pressure and cardiac contraction during lipopolysaccharide challenge

In the present study, we used the Langendorff technique to evaluate the involvement of endothelin-1 (ET-I) and nitric oxide (NO) in coronary vasoconstriction and myocardial depression in hearts isolated from lipopolysaccharide (LPS)-treated rats. Coronary perfusion pressure (CPP) increased markedly in hearts from LPS -treated rats. Pretreatment with BQ-123, an ET-1 type A receptor antagonist, significantly reduced the increase in CPP induced by LPS. LPS induced a marked decrease in left ventricular developed pressure, the product of left ventricular developed pressure and heart rate, as well as the maximal rate of rise/fall of left ventricular pressure. Pretreatment with BQ-123 partially reversed the LPS-induced cardiac depression. Administration of BQ-123 and AMG, an inhibitor of iNOS, prior to LPS challenge significantly blocked the negative inotropic effect. These results suggest that ET-1 augments the NO-mediated cardiac contractile depression induced by LPS and the accompanying increase in coronary resistance.