From molecules to mammals: what's NOS got to do with it?

Area of Science:

• Biochemistry
• Physiology
• Genetics

Background:

• Nitric oxide synthases (NOSs) catalyze the production of nitric oxide (NO) and l-citrulline from l-arginine and oxygen.
• Three mammalian NOS genes exist: neuronal NOS (nNOS/NOS1), inducible NOS (iNOS/NOS2), and endothelial NOS (eNOS/NOS3).
• The structure, function, and pharmacology of NOS enzymes are well-characterized, indicating vital roles in numerous biological systems.

Purpose of the Study:

• To review the contributions of knockout and transgenic mouse models to understanding NOS enzyme function.
• To focus on the interplay between NOS enzymes and the pathophysiology of the vascular system.
• To highlight the translation of genomic data into physiological insights for health and biology.

Main Methods:

• Utilizing data from complementary knockout and transgenic over-expression mouse models.
• Analyzing the established knowledge on NOS enzyme structure, enzymology, and pharmacology.
• Reviewing studies that investigate the roles of NOS in neuronal, renal, pulmonary, gastro-intestinal, skeletal muscle, reproductive, and cardiovascular biology.

Main Results:

• Knockout and transgenic mouse models have significantly advanced the understanding of NOS roles in diverse biological processes.
• These models have revealed critical functions of NOS in cardiovascular biology.
• The studies underscore the importance of NOS enzymes in maintaining vascular homeostasis and their involvement in vascular diseases.

Conclusions:

• Mouse models are invaluable tools for dissecting the complex roles of NOS enzymes in health and disease.
• Further research translating genomic insights into physiological understanding of NOS is crucial for advancing healthcare.
• The NOS system plays a pivotal role in vascular pathophysiology, with significant implications for therapeutic strategies.