ABSTRACT
BACKGROUND: Bradykinin (BK) is a key mediator regulating coronary blood flow. It is degraded by angiotensin-converting enzyme (ACE), but what is unknown is whether enhanced tissue ACE activity interferes with BK-induced coronary vasodilation in obesity. METHODS AND RESULTS: Coronary arterioles (~100 µm) were isolated from rats on a normal or high-fat diet (HFD) and from lean or obese patients undergoing heart surgery (n=74). We found that BK-induced dilation was diminished in the coronary arterioles of HFD rats, when compared with controls. When administered in vitro, the ACE inhibitor, captopril, restored the coronary dilation response to BK in HFD rats, but did not affect control responses. Abundant ACE expression was detected in coronary endothelium, which was associated with increased ACE activity in HFD arterioles, as measured by increased response to the ACE substrate, angiotensin I. Moreover, we found that in the coronary arterioles of obese patients, BK-induced dilation was augmented by in vitro captopril administration. Correspondingly, ACE activity was increased in the coronary arterioles of obese patients when compared with the non-obese. Logistic regression analysis revealed that obese patients taking ACE inhibitors prior to surgery exhibited an enhanced dilation response to BK. CONCLUSIONS: We demonstrated augmented tissue ACE activity in the coronary arterioles of obese subjects, which leads to reduced coronary dilation response to BK. We provide a rationale for ACE inhibitor therapy in obese patients to improve dilatation of coronary microvessels.
Subject(s)
Bradykinin/pharmacology , Coronary Vessels , Endothelium, Vascular , Peptidyl-Dipeptidase A/metabolism , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Aged , Angiotensin I/metabolism , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Animals , Arterioles/enzymology , Arterioles/physiopathology , Bradykinin/metabolism , Captopril/administration & dosage , Coronary Vessels/enzymology , Coronary Vessels/physiology , Endothelium, Vascular/enzymology , Endothelium, Vascular/physiopathology , Female , Gene Expression Regulation, Enzymologic/drug effects , Humans , Male , Middle Aged , Rats , Rats, Wistar , Vasodilator Agents/metabolismABSTRACT
We present a case of thoracic splenosis diagnosed by tru-cut needle biopsy, which yielded histologically normal splenic tissue. This is the first report of a diagnosis of thoracic splenosis by needle biopsy. The patient had a history characteristic of thoracic splenosis. Autotransplanted splenic tissue functions and may provide some defense against serious infections. A conservative approach to diagnosis offers the advantages of preserving splenic tissue and avoiding thoracotomy.
