Nitric oxide signalling in kidney regulation and cardiometabolic health

Area of Science:

• Physiology
• Biochemistry
• Pathophysiology

Background:

• Cardiovascular, metabolic, and kidney diseases are increasing globally, causing significant morbidity, mortality, and economic burden.
• Compromised nitric oxide (NO) bioactivity, linked to oxidative stress, is a key proposed mechanism in these disorders.
• The L-arginine-dependent nitric oxide synthase (NOS) pathway, the primary source of endogenous NO, is often impaired in these pathologies.

Purpose of the Study:

• To explore the role of compromised NO bioactivity in cardiovascular, metabolic, and kidney diseases.
• To investigate the potential of the nitrate-nitrite-NO pathway as an alternative source of NO.
• To highlight novel therapeutic strategies for restoring NO homeostasis.

Main Methods:

• Review of existing literature on nitric oxide pathways and related diseases.
• Analysis of the mechanisms underlying NO deficiency and oxidative stress.
• Evaluation of the nitrate-nitrite-NO pathway's role in NO formation.

Main Results:

• The L-arginine-NOS pathway is frequently compromised in cardiovascular, metabolic, and kidney diseases.
• The nitrate-nitrite-NO pathway provides an alternative route for NO generation, independent of NOS.
• Signaling through this pathway involves both cGMP-dependent and independent mechanisms.

Conclusions:

• Restoring NO homeostasis is crucial for managing cardiovascular, metabolic, and kidney disorders.
• The nitrate-nitrite-NO pathway presents a promising therapeutic target for conditions with NOS deficiency and oxidative stress.
• Novel approaches targeting this pathway could lead to effective preventive and therapeutic interventions.