Phenylephrine and endothelin differentially stimulate cardiac PI hydrolysis and ANF expression

Area of Science:

• Cardiology
• Molecular Biology
• Cell Signaling

Background:

• Phenylephrine (PE) and endothelin (ET) are known to stimulate phosphoinositide (PI) hydrolysis, cell growth, and gene expression, including atrial natriuretic factor (ANF), in ventricular myocytes, processes linked to cardiac hypertrophy.
• Understanding the long-term effects of these agonists is crucial for elucidating mechanisms of cardiac remodeling.

Purpose of the Study:

• To investigate and compare the long-term effects of phenylephrine (PE) and endothelin (ET) on cardiac second messenger production and gene expression.
• To determine if the cellular responses to PE and ET diverge over extended exposure periods (up to 72 hours).

Main Methods:

• Ventricular myocytes were exposed to PE or ET for up to 72 hours.
• Production of inositol monophosphate (InsP) and diglyceride (DG), products of PI hydrolysis, was measured.
• Expression of atrial natriuretic factor (ANF) was monitored over the time course.

Main Results:

• PE consistently stimulated InsP production and maintained elevated DG levels throughout the 72-hour period, with sustained ANF production from 24 to 72 hours.
• ET initially produced similar InsP and DG responses to PE, but these diminished by 24 hours.
• ET-stimulated ANF production peaked at 24 hours and declined by 72 hours.
• Desensitization to ET did not affect the response to PE, indicating ET-specific desensitization.

Conclusions:

• While PE and ET share initial stimulatory effects on cardiac second messengers and ANF expression, their effects diverge significantly with prolonged exposure.
• These findings highlight distinct, hormonally specific signaling pathways and temporal patterns for PE and ET in ventricular myocytes during extended stimulation.
• The results provide insights into the differential regulation of cardiac hypertrophy-associated genes by various agonists over time.