Dysregulated mitogen-activated protein kinase and matrix metalloproteinase in ethanol-induced cavernosal dysfunction

Area of Science:

• Physiology
• Biochemistry
• Pharmacology

Background:

• Ethanol's effects on penile smooth muscle function are not fully understood.
• Mitogen-activated protein kinases (MAPK) and matrix metalloproteinases (MMP) are critical in regulating smooth muscle function.
• Investigating these pathways may reveal mechanisms underlying ethanol-induced erectile dysfunction.

Purpose of the Study:

• To investigate the impact of chronic ethanol consumption on MAPK and MMP pathways in rat cavernosal smooth muscle (CSM).
• To determine the role of the SAPK/JNK pathway in ethanol's effects on CSM contractility.
• To assess changes in circulating MMP levels following ethanol treatment.

Main Methods:

• Male Wistar rats were treated with ethanol (20% v/v) for 6 weeks.
• Quantitative real-time PCR and Western immunoblotting were used to analyze MAPK and MMP expression and phosphorylation.
• Functional assays with SP600125 (SAPK/JNK inhibitor) and measurement of MMP activity and circulating levels were performed.

Main Results:

• Ethanol did not alter mRNA levels of p38MAPK, SAPK/JNK, ERK1/2, MMP-2, or MMP-9.
• Ethanol decreased protein expression of p38MAPK, MMP-2, and increased SAPK/JNK phosphorylation in CSM.
• Ethanol decreased MMP-2 activity, increased circulating MMP-2, MMP-9, TIMP-2, and the MMP-9/TIMP-1 ratio.
• SAPK/JNK inhibition prevented ethanol-induced increases in endothelin-1 mediated contraction.

Conclusions:

• Ethanol consumption down-regulates MAPK and MMP pathways in rat CSM.
• Ethanol increases circulating MMP-9 levels.
• The SAPK/JNK pathway is implicated in ethanol-induced alterations of CSM contractility.