A missing link between a high salt intake and blood pressure increase.
It is widely accepted that a high sodium intake triggers blood pressure rise. However, only one-third of the normotensive subjects were reported to show salt-sensitivity in their blood pressure. Many factors have been proposed as causes of salt-sensitive hypertension, but none of them provides a satisfactory explanation. We propose, on the basis of accumulated data, that the reduced activity of the kallikrein-kinin system in the kidney may provide this link. Renal kallikrein is secreted by the distal connecting tubular cells and all kallikrein-kinin system components are distributed along the collecting ducts in the distal nephron. Bradykinin generated is immediately destroyed by carboxypeptidase Y-like exopeptidase and neutral endopeptidase, both quite independent from the kininases in plasma, such as angiotensin converting enzyme. The salt-sensitivity of the blood pressure depends largely upon ethnicity and potassium intake. Interestingly, potassium and ATP-sensitive potassium (K(ATP)) channel blockers accelerate renal kallikrein secretion and suppress blood pressure rises in animal hypertension models. Measurement of urinary kallikrein may become necessary in salt-sensitive normotensive and hypertensive subjects. Furthermore, pharmaceutical development of renal kallikrein releasers, such as K(ATP) channel blockers, and renal kininase inhibitors, such as ebelactone B, may lead to the development of novel antihypertensive drugs.
Katori
Makoto
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan. hy3m_ktr@asahi-net.or.jp
Majima
Masataka
M
D001741:Black or African American / Q000235:genetics; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D003900:Desoxycorticosterone / Q000633:toxicity; D005544:Forecasting; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000378:metabolism*; D008954:Models, Biological; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000097:blood / Q000652:urine; D012965:Sodium Chloride / Q000008:administration & dosage / Q000633:toxicity; D012982:Sodium, Dietary / Q000009:adverse effects*
D000959:Antihypertensive Agents; D012982:Sodium, Dietary; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D012964:Sodium; D011188:Potassium