Reduced Activity of the Aortic Gamma-Glutamyltransferase Does Not Decrease S-Nitrosoglutathione Induced...

Area of Science:

• Cardiovascular Science
• Enzymology
• Physiology

Background:

• Gamma-glutamyl transferase (GGT) plays a role in nitric oxide (NO) release from S-nitrosoglutathione (GSNO), influencing vasodilation.
• Decreased NO bioavailability is a hallmark of cardiovascular diseases, making exogenous GSNO a potential therapeutic agent.
• The spontaneous hypertensive rat (SHR) model is used to study hypertension and its effects on vascular function.

Purpose of the Study:

• To investigate the impact of reduced vascular GGT activity on the vasorelaxant effects of GSNO in a rat model of hypertension.
• To assess whether a high salt diet exacerbates these changes in hypertensive rats.

Main Methods:

• Thoracic aortic rings from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were used.
• Vascular reactivity to carbachol, sodium nitroprusside, and GSNO was measured.
• GGT activity was quantified, and its role in GSNO-induced relaxation was assessed using enzyme inhibition.
• The involvement of protein disulfide isomerase (PDI) in GSNO metabolism was also evaluated.

Main Results:

• Aortic GGT activity was significantly decreased in SHR, with further reduction in SHR on a high salt diet.
• Endothelial-dependent vasodilation was slightly impaired in SHR.
• Despite reduced GGT activity, sensitivity to GSNO was slightly enhanced in SHR.
• The contribution of GGT and PDI to GSNO effects remained similar across all groups.

Conclusions:

• Hypertension is associated with reduced aortic GGT activity.
• The vasorelaxant effects of GSNO are not diminished in hypertension, suggesting compensatory mechanisms.
• Protein disulfide isomerase (PDI) may play an alternative role in maintaining GSNO bioactivity in the context of decreased GGT activity.