Neuronal nitric oxide synthase in hypertension - an update

Area of Science:

• Cardiovascular Research
• Molecular Cardiology
• Hypertension Pathophysiology

Background:

• Hypertension is a major risk factor for cardiovascular diseases, linked to reduced nitric oxide (NO) bioavailability.
• NO deficiency in the heart exacerbates pressure-overload, leading to cardiac hypertrophy, fibrosis, and heart failure.
• Both endothelial (eNOS) and neuronal (nNOS) nitric oxide synthases are key NO sources in the myocardium, with nNOS regulating crucial cellular functions.

Approach:

• This review examines recent findings on the upstream and downstream regulation of cardiac nNOS in hypertension.
• It investigates the mechanisms underlying nNOS induction by angiotensin II (Ang II) via AT1R and AT2R.
• The role of NADPH oxidase and ROS-dependent eNOS activity in nNOS regulation is also explored.

Key Points:

• Cardiac eNOS protein is reduced, while nNOS expression and activity increase in hypertensive hearts.
• nNOS induction involves a complex interplay between Ang II receptors (AT1R/AT2R), NADPH oxidase, and ROS-dependent eNOS activity.
• nNOS offers cardioprotection in hypertension through positive lusitropy and novel signaling pathways involving sGC-cGMP/PKG.

Conclusions:

• Understanding the regulation of cardiac nNOS in hypertension is crucial for developing new therapeutic strategies.
• Targeting nNOS pathways may offer a novel approach to treating hypertensive cardiomyopathy.
• Further research into nNOS mechanisms could lead to treatments for heart failure and sudden cardiac death associated with hypertension.