Endothelin regulates angiotensin-converting enzyme in the mouse kidney

Area of Science:

• Physiology
• Pharmacology
• Biochemistry

Background:

• Endothelin-1 (ET-1) plays a role in regulating cardiovascular function.
• Angiotensin-converting enzyme (ACE) is a key component of the renin-angiotensin system.
• The influence of dietary fat on ACE regulation in vivo is not fully understood.

Purpose of the Study:

• To investigate the role of ET-1 and dietary fat in the in vivo regulation of ACE activity.
• To determine if ET-1 antagonism affects ACE activity in the context of a high-fat diet.

Main Methods:

• Utilized C57BL6/J mice fed a Western-type diet.
• Administered the endothelin-A (ETA) receptor antagonist LU135252.
• Measured renal and pulmonary ACE activity, ACE mRNA expression, renal ET-1 protein, and nitrite/nitrate levels.

Main Results:

• A Western-type diet significantly increased renal ACE activity and renal ET-1 levels.
• Chronic treatment with LU135252 completely prevented the diet-induced increase in renal ACE activity.
• LU135252's effect on ACE activity was independent of changes in ACE mRNA expression or renal ET-1 protein levels.

Conclusions:

• Dietary fat activates renal ACE activity.
• ET-1 is involved in the regulation of tissue ACE activity in vivo.
• ET-1's regulatory role in ACE activity occurs independently of ACE mRNA expression.