Increased tissue angiotensin-converting enzyme activity impairs bradykinin-induced dilation of coronary arterioles in obesity.
Study Goal
The researchers aimed to determine whether enhanced tissue ACE activity in obesity interferes with bradykinin-induced coronary vasodilation and if ACE inhibitors could restore this response.
Results Summary
The study found that high-fat diet (HFD) reduced bradykinin-induced dilation in coronary arterioles in rats and obese patients, which was restored by ACE inhibitors. Increased ACE activity was observed in HFD and obese subjects, suggesting a rationale for ACE inhibitor therapy in obesity.
Population
Rats on normal or high-fat diet and lean or obese patients undergoing heart surgery (n=74).
Effective Dosage
Not specified
Duration
Not specified
Interactions
ACE inhibitors (captopril) improved dilation response in obese subjects.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
high-fat diet | decrease | BK-induced dilation | HFD rats | - | diminished | #1 |
captopril | increase | coronary dilation response to BK | HFD rats | - | restored | #2 |
captopril | no change | control responses | control rats | - | did not affect | #3 |
high-fat diet | increase | ACE activity | HFD arterioles | - | increased | #4 |
captopril | increase | BK-induced dilation | obese patients | - | augmented | #5 |
obesity | increase | ACE activity | coronary arterioles of obese patients | - | increased | #6 |
ACE inhibitors | increase | dilation response to BK | obese patients taking ACE inhibitors prior to surgery | - | exhibited an enhanced | #7 |
augmented tissue ACE activity | decrease | coronary dilation response to BK | obese subjects | - | leads to reduced | #8 |
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.