Related Experiment Videos
The renin-angiotensin system in the heart and vascular wall: new therapeutic aspects
M Falkenhahn1, P Gohlke, M Paul
1Department of Pharmacology, University of Heidelberg, Germany.
Abstract:
Traditionally, the renin-angiotensin system (RAS) has been viewed as an endocrine system. Recently, independent tissue RASs have been postulated that are believed to act in a paracrine/autocrine fashion. Elements of the RAS have been shown to exist in many peripheral tissues. Angiotensin-converting enzyme (ACE), a key element of the RAS, is found mainly in the vascular endothelium and therefore represents the main target site for inhibition of the local and circulating RASs. In the heart, angiotensin II exerts a direct positive inotropic and chronotropic effect. More recently, it was also found that angiotensin II may act as a growth factor in several cell types. Angiotensin II is also thought to be partially responsible for structural remodeling in cardiac hypertrophy. The role of ACE inhibitors has been established in the treatment of hypertension and congestive heart failure. Recent multicenter trials revealed a beneficial role of ACE inhibitors in reduction of mortality rates in patients with congestive heart failure and a low ejection fraction. Mechanisms that include reduction of myocardial oxygen demand, improvement of coronary blood flow, induction of capillary proliferation, reduction of blood pressure and ventricular wall tension without reflex tachycardia, and impairment of myocardial contractility are the basis for the beneficial effects of ACE inhibitors. In addition to a reduction of angiotensin II generation, these effects appear to be largely brought about by the inhibition of endogenous kinin degradation. Recent studies suggest that a deletion polymorphism in the gene encoding ACE is a risk factor in myocardial infarction (MI).(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Angiotensin-converting enzyme (ACE) inhibitors benefit heart failure patients by reducing mortality. They work by inhibiting the renin-angiotensin system (RAS) and improving cardiac function.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
Background:
- The renin-angiotensin system (RAS) traditionally viewed as endocrine, now includes local tissue-specific systems.
- Angiotensin-converting enzyme (ACE) is crucial in RAS, primarily in vascular endothelium, making it a key therapeutic target.
- Angiotensin II in the heart has positive inotropic/chronotropic effects and acts as a growth factor, contributing to cardiac hypertrophy.
Purpose of the Study:
- To review the established and emerging roles of ACE inhibitors in cardiovascular medicine.
- To elucidate the mechanisms behind the beneficial effects of ACE inhibitors in heart failure.
- To discuss the significance of ACE gene polymorphism in myocardial infarction risk.
Main Methods:
- Review of existing literature and multicenter trial data on ACE inhibitors.
- Analysis of the physiological effects of angiotensin II and ACE inhibition on cardiac function.
- Examination of genetic factors, specifically ACE gene polymorphism, related to cardiovascular events.
Main Results:
- ACE inhibitors are established treatments for hypertension and congestive heart failure.
- Recent trials show ACE inhibitors reduce mortality in heart failure patients with low ejection fraction.
- ACE inhibitors offer benefits through reduced myocardial oxygen demand, improved coronary flow, and blood pressure regulation.
Conclusions:
- ACE inhibitors provide significant survival benefits in heart failure patients.
- Mechanisms include direct cardiac effects and inhibition of kinin degradation.
- ACE gene polymorphism may be a risk factor for myocardial infarction.