Cross-tolerance between endogenous nitric oxide and exogenous nitric oxide donors

Area of Science:

• Cardiovascular Biology
• Pharmacology
• Cellular Physiology

Background:

• Nitric oxide (NO) plays a crucial role in vascular homeostasis.
• The development of tolerance to NO donors is not fully understood.
• Investigating cross-tolerance is essential for understanding NO signaling pathways.

Purpose of the Study:

• To determine if cross-tolerance develops between endogenous NO and exogenous NO donors.
• To investigate the mechanisms of tolerance in aortic smooth muscle cells.
• To assess the impact of inflammatory stimuli on NO-induced responses.

Main Methods:

• Cultured aortic smooth muscle cells from various species (human, rat, rabbit, porcine, bovine) were used.
• cGMP accumulation was measured following exposure to sodium nitroprusside (SNP) and other NO donors.
• Cross-tolerance was assessed using different NO-releasing agents and co-culture models.

Main Results:

• Sodium nitroprusside induced a time- and concentration-dependent tolerance in smooth muscle cells.
• Cross-tolerance was observed between SNP and S-nitroso-N-acetylpenicillamine, but not atriopeptin.
• Endotoxin and IL-1beta pre-treatment reduced SNP-induced cGMP accumulation.
• Pre-exposure to SNP decreased responsiveness to endothelium-derived NO in co-cultures.

Conclusions:

• Cross-tolerance between endothelium-derived NO and exogenous NO donors occurs in vitro.
• Aortic smooth muscle cells can develop tolerance to NO signaling.
• These findings have implications for understanding vascular function and therapeutic interventions involving NO.