Renal kininases in primary aldosteronism

Area of Science:

• Nephrology
• Endocrinology
• Biochemistry

Background:

• The renal kallikrein-kinin (K-K) system plays a crucial role in regulating blood pressure and fluid balance.
• Primary aldosteronism (PA) is characterized by excessive aldosterone production, leading to hypertension and electrolyte imbalances.
• The specific involvement of the renal K-K system in the pathophysiology of PA remains incompletely understood.

Purpose of the Study:

• To investigate the role of the renal K-K system in primary aldosteronism (PA).
• To quantify daily urinary excretions of K-K system components in PA patients and normotensive controls (NT).
• To establish and utilize a novel method for simultaneous determination of urinary kininase I, II, and neutral endopeptidase (NEP).

Main Methods:

• Collected 24-hour urine samples from patients with PA and NT individuals.
• Measured urinary kallikrein (KAL), kinin (KIN), total kininase (K-ase), K-ase I, K-ase II, and NEP.
• Employed a newly developed method for simultaneous quantification of urinary K-ase I, II, and NEP.

Main Results:

• Urinary KAL excretion was significantly higher in PA compared to NT.
• No significant difference in urinary KIN excretion was observed between PA and NT groups.
• Total K-ase and NEP activities were significantly elevated in PA patients compared to NT.
• Urinary K-ase I and K-ase II levels did not differ between PA and NT groups.
• NEP constituted a larger proportion of total K-ase activity in NT (59%) than in PA (36%), with unknown kininases accounting for the remainder in PA.

Conclusions:

• Neutral endopeptidase (NEP) is likely a major enzyme in renal kinin catabolism in humans.
• NEP activity is accelerated in primary aldosteronism (PA).
• The findings suggest the presence of unidentified kininases in PA, contributing to accelerated renal kininase activity.
• Elevated renal kininase activity may contribute to the renal water-sodium metabolism disorder and hypertension observed in PA.