Related Experiment Videos
Effects of angiotensin-converting enzyme inhibitors on tissue renin-angiotensin systems
1German Institute for High Blood Pressure Research, University of Heidelberg.
Insights
The renin-angiotensin system (RAS) controls blood pressure. Tissue-specific RAS inhibition may be more effective than systemic inhibition for treating cardiovascular disorders like heart failure.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Pharmacology
Background:
- The renin-angiotensin system (RAS) is crucial for blood pressure regulation and cardiovascular homeostasis.
- Angiotensin-converting enzyme (ACE) inhibitors are widely used for hypertension and heart failure.
- Evidence suggests a local tissue RAS operates independently from the plasma RAS.
Purpose of the Study:
- To explore the significance of tissue-specific RAS.
- To evaluate the potential of tissue ACE inhibition in cardiovascular disease treatment.
- To differentiate the roles of plasma and tissue RAS in cardiovascular regulation.
Main Methods:
- Review of experimental and clinical findings on RAS components and ACE inhibitors.
- Analysis of the expression and function of RAS in extrarenal tissues.
- Comparison of the effects of circulating versus tissue ACE inhibition.
Main Results:
- Local generation of angiotensin II confirms the existence of a tissue RAS.
- Tissue RAS may have organ-specific functions, distinct from plasma RAS.
- Tissue RAS is implicated in chronic conditions like cardiac hypertrophy and atherosclerosis.
Conclusions:
- Tissue ACE inhibition may be more important than systemic inhibition for treating heart failure.
- Local RAS influences chronic cardiovascular structural changes and pathogenesis.
- ACE inhibitors may exert long-term antihypertensive effects by inhibiting tissue RAS.
Abstract:
The renin-angiotensin system (RAS) plays a major role in the control of blood pressure and cardiovascular homeostasis and is involved in the pathogenesis of a number of cardiovascular disorders. The efficacy of angiotensin-converting enzyme (ACE) inhibitors in the treatment of hypertension and congestive heart failure has led to the widespread clinical use of ACE inhibitors in primary or secondary prevention of heart disease. The demonstration of the expression of the components of the RAS in several extrarenal tissues, as well as local generation of angiotensin II, has confirmed the existence of a tissue RAS that may serve organ-specific functions and act independently from the plasma RAS. The concept of paracrine/autocrine functions of the local RAS has changed our understanding of the functions of the RAS and suggests that tissue ACE inhibition may be of greater importance than inhibition of circulating ACE in the treatment of congestive heart failure and other cardiovascular disorders. Whereas the circulating endocrine RAS appears to be responsible for mediation of acute effects, the tissue RAS seems to be involved in more chronic situations, such as secondary structural changes of the cardiovascular system, and therefore could contribute to the pathogenesis of hypertension as well as other cardiovascular disorders, such as cardiac hypertrophy, coronary artery disease, and atherosclerosis. Several experimental and clinical findings suggest that reversal of cardiovascular structural changes secondary to cardiovascular disease and enhancement of renal sodium excretion by ACE inhibitors are important long-term antihypertensive actions possibly mediated by inhibition of the tissue RAS.