Role of intracardiac angiotensin II in cardiac dysfunction of rat during septic shock.
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.
Ji
Y
Y
Department of Pathophysiology, Beijing Medical University.
Ren
X
X
Zhao
Y
Y
Dong
L
L
Wu
L
L
Su
J
J
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002303:Cardiac Output, Low / Q000209:etiology / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000150:complications / Q000378:metabolism*
D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A