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


CONCLUSIONS
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.
Azizi
Michel
M
Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, F-75015 France. michel.azizi@egp.aphp.fr
Emanueli
Costanza
C
Peyrard
Severine
S
Maddedu
Paolo
P
Alhenc-Gelas
François
F
Campbell
Duncan J
DJ
D000222:Adaptation, Physiological; D018592:Cross-Over Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007668:Kidney / Q000378:metabolism*; D007705:Kinins / Q000378:metabolism / Q000652:urine*; D008297:Male; D011110:Polymorphism, Genetic; D017419:Potassium, Dietary / Q000494:pharmacology*; D012982:Sodium, Dietary / Q000494:pharmacology*; D020840:Tissue Kallikreins / Q000097:blood* / Q000235:genetics* / Q000378:metabolism
D007705:Kinins; D017419:Potassium, Dietary; D012982:Sodium, Dietary; D020840:Tissue Kallikreins