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Genetic and dietary control of plasma tissue kallikrein secretion and urinary kinins exretion in man

2008; Lippincott Williams & Wilkins; Volume: 26; Issue: 4 Linguagem: Inglês

10.1097/hjh.0b013e3282f4d1fa

1473-5598

Michel Azizi, Costanza Emanueli, Séverine Peyrard, Paolo Maddedu, François Alhenc–Gelas, Duncan J. Campbell,

Renin-Angiotensin System Studies

Objectives Tissue kallikrein is a major kinin-forming enzyme involved in artery and kidney functions. Urinary tissue kallikrein activity (UKLKa) reflects renal tissue kallikrein activity and depends on Na and K intake, and genetic factors, especially the tissue kallikrein-inactivating polymorphism, R53H. The effect of these factors on the level of kinin peptides is, however, not known. Moreover, a circulating form of tissue kallikrein is present in human plasma but its origin and regulation are unknown. Methods We used a crossover study to investigate UKLKa, plasma tissue kallikrein (pTK), and urinary kallidin peptides and metabolites (Uki) in 10 R53H and 30 R53R normotensive male subjects randomly assigned to either a 1-week low Na–high K or a high Na–low K diet. Results UKLKa was 50–60% lower in R53H than R53R subjects and was increased by the low Na–high K diet. pTK was also 45–55% lower in R53H than R53R subjects and was increased by the low Na–high K diet. Uki was slightly but significantly higher under the low Na–high K than the high Na–low K diet, but did not differ between genotypes. Conclusion These observations indicate that pTK levels are genetically determined and regulated by Na and K diet, in parallel with UKLKa; this suggests that circulating tissue kallikrein originates mainly from the kidney, and can contribute to circulatory adaptation to dietary ions. Uki is influenced by the Na and K diet, suggesting that kinins participate in renal adaptation to ion intake, but do not quantitatively reflect tissue kallikrein activity in urine, or presumably, in the kidney.