Diminished L-arginine bioavailability in hypertension

Area of Science:

• Cardiovascular Physiology
• Molecular Transport Mechanisms
• Biochemistry of Hypertension

Background:

• L-Arginine is crucial for nitric oxide (NO) production, essential for vascular relaxation and platelet function.
• The 'L-arginine paradox' highlights the importance of L-arginine transport for NO synthesis, even when intracellular concentrations are high.
• Systemic arterial hypertension may involve dysregulation of the L-arginine/NO pathway.

Purpose of the Study:

• To investigate the modulation of the L-arginine/NO pathway in systemic arterial hypertension.
• To analyze L-arginine transport, NO synthase (NOS) activity, and plasma amino acid profiles in hypertensive patients and a relevant animal model.

Main Methods:

• Analysis of L-arginine transport into red blood cells (RBCs) and platelets using specific cationic amino acid transport systems (y+ and y+L).
• Measurement of basal NO synthase (NOS) activity in platelets.
• Chromatographic analysis of plasma amino acid profiles.
• Studies conducted in hypertensive patients and spontaneously hypertensive rats.

Main Results:

• Plasma L-arginine levels were higher in hypertensive patients compared to controls.
• L-Arginine transport via system y+L was significantly reduced in RBCs and platelets of hypertensive individuals and in RBCs of hypertensive rats.
• Basal NOS activity was decreased in platelets from hypertensive patients.
• Hypertension is associated with reduced L-arginine availability for NO synthesis in blood cells.

Conclusions:

• Hypertension is characterized by impaired L-arginine transport, specifically via system y+L, in both human and animal blood cells.
• This reduced transport limits the availability of L-arginine for nitric oxide synthesis.
• The findings elucidate a novel mechanism contributing to endothelial dysfunction and platelet abnormalities in hypertension.