On the local cardiac renin angiotensin system. Basic and clinical implications

Area of Science:

• Cardiovascular Physiology
• Renal Physiology
• Molecular Cardiology

Background:

• The heart possesses a local renin-angiotensin system (RAS).
• An intracrine component of the cardiac RAS is activated during pathological conditions such as heart failure and hypertension.
• Existing research suggests implications for cardiovascular disease management.

Purpose of the Study:

• To reevaluate experimental and clinical evidence for a local cardiac RAS.
• To discuss the role of the intracrine cardiac RAS in heart failure and hypertension.
• To explore novel findings regarding cell swelling, cardiac arrhythmias, and AT1 receptor function.

Main Methods:

• Review of existing experimental and clinical evidence.
• Analysis of the functional intracrine component of the cardiac RAS.
• Evaluation of the role of salt loading in activating the cardiac RAS.

Main Results:

• Cell swelling impairs cell coupling and impulse propagation via ionic channels, leading to cardiac arrhythmias.
• Angiotensin II (Ang II) type 1 (AT1) receptors function as mechanosensors, altering heart function independently of Ang II.
• Salt loading activates the local cardiac renin-angiotensin system, with significant consequences for heart function.

Conclusions:

• The local cardiac renin-angiotensin system, including its intracrine component, plays a critical role in cardiovascular pathology.
• Novel mechanisms involving cell swelling and AT1 receptor mechanosensing contribute to cardiac dysfunction and arrhythmias.
• Understanding these pathways offers potential therapeutic targets for heart failure and hypertension.