The heart as an endocrine gland

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Molecular Biology

Background:

• Atrial natriuretic factor (ANF) is a hormone primarily known for its role in cardiovascular regulation.
• The complete structure and gene of ANF have been elucidated in rats and humans.
• ANF and its messenger RNA are expressed not only in the atria but also in the ventricles.

Purpose of the Study:

• To characterize the structure and processing of atrial natriuretic factor (ANF).
• To investigate the cellular mechanisms of ANF action.
• To examine the role of ANF in experimental hypertension and heart failure.

Main Methods:

• Sequence determination of ANF, rat and human cDNA, and gene.
• Isolation and characterization of an ANF-cleaving enzyme (IRCM-SP1) from cardiac tissue.
• Measurement of cyclic guanosine 3',5'-monophosphate (cGMP) and cyclic adenosine 3',5'-monophosphate (cAMP) levels.
• In vitro and in vivo studies on ANF's effects on vascular smooth muscle, steroidogenesis, and arginine vasopressin (AVP) release.
• Analysis of ANF levels in various models of experimental hypertension and heart failure.

Main Results:

• The circulating form of ANF is the C-terminal fragment (Ser 99-Tyr 126).
• A specific enzyme (IRCM-SP1) cleaves pro-ANF into various active fragments.
• ANF modulates intracellular signaling pathways, increasing cGMP and decreasing cAMP.
• ANF causes vasodilation, inhibits steroidogenesis, and affects AVP release.
• Plasma ANF levels are elevated in experimental hypertension, and ANF infusion lowers blood pressure.
• In heart failure, atrial ANF is decreased, while plasma and ventricular ANF are increased.

Conclusions:

• ANF is processed by a specific cardiac enzyme, yielding biologically active fragments.
• ANF plays a significant role in regulating blood pressure and fluid balance, particularly in hypertensive states.
• Alterations in ANF levels are associated with cardiovascular diseases like hypertension and heart failure.