OBJECTIVE: To observe changes in the content of myocardial angiotensin II and its role in cardiac dysfunction of rat during septic shock. METHODS: Septic shock model was produced by cecal ligation and puncture (CLP) operation on rats. Experimental rats were given captopril 15 mg.kg-1/d per os for 3 days before CLP operation. Mean blood pressure and left ventricular pressure were recorded. Myocardial angiotensin converting enzyme (ACE) activities were determined by a fluorometric assay and myocardial angiotensin II content was measured by radioimmunoassay. Highly purified membrane of sarcoplasmic reticulum (SR) was prepared from rat hearts. Assays were made of ATP-dependent Ca2+ uptake by cardiac SR and (3H) ryanodine binding to SR. RESULTS: Myocardial angiotensin II content increased by 51.5% (P < 0.01) at the 18th hour post CLP, meanwhile there was a decrease in left ventricular +/- dp/dtmax value and the impairment in Ca2+ uptake and (3H) ryanodine binding to cardiac SR. Preliminary administration of captopril reduced myocardial ACE activity and angiotensin II content, but increased left ventricular +/- dp/dtmax value. In comparison to shock group, the initial rate and the capacity of SR Ca2+ uptake were increased by 120% (P < 0.01) and 33.9% (P < 0.05), the Bmax value of (3H) ryanodine binding to SR was also elevated, while the Kd value remained unchanged. CONCLUSIONS: The elevated intracardiac angiotensin II, resulting from the activation of myocardial ACE during sepsis, probably serves as one of the important mediators participating in the pathogenesis of heart failure: the effects of angiotensin II may be associated with the disturbance of Ca2+ transport function of cardiac SR.
OBJECTIVE: To observe changes in the content of myocardial angiotensin II and its role in cardiac dysfunction of rat during septic shock. METHODS:Septic shock model was produced by cecal ligation and puncture (CLP) operation on rats. Experimental rats were given captopril 15 mg.kg-1/d per os for 3 days before CLP operation. Mean blood pressure and left ventricular pressure were recorded. Myocardial angiotensin converting enzyme (ACE) activities were determined by a fluorometric assay and myocardial angiotensin II content was measured by radioimmunoassay. Highly purified membrane of sarcoplasmic reticulum (SR) was prepared from rat hearts. Assays were made of ATP-dependent Ca2+ uptake by cardiac SR and (3H) ryanodine binding to SR. RESULTS: Myocardial angiotensin II content increased by 51.5% (P < 0.01) at the 18th hour post CLP, meanwhile there was a decrease in left ventricular +/- dp/dtmax value and the impairment in Ca2+ uptake and (3H) ryanodine binding to cardiac SR. Preliminary administration of captopril reduced myocardial ACE activity and angiotensin II content, but increased left ventricular +/- dp/dtmax value. In comparison to shock group, the initial rate and the capacity of SR Ca2+ uptake were increased by 120% (P < 0.01) and 33.9% (P < 0.05), the Bmax value of (3H) ryanodine binding to SR was also elevated, while the Kd value remained unchanged. CONCLUSIONS: The elevated intracardiac angiotensin II, resulting from the activation of myocardial ACE during sepsis, probably serves as one of the important mediators participating in the pathogenesis of heart failure: the effects of angiotensin II may be associated with the disturbance of Ca2+ transport function of cardiac SR.