An ATP-sensitive potassium channel blocker suppresses sodium-induced hypertension through increased secretion of urinary kallikrein.
It is suggested that an ATP-sensitive potassium channel blocker suppresses sodium-induced hypertension through increased secretion of urinary kallikrein. We reported that glibenclamide, an ATP-sensitive potassium channel blocker, accelerated dose-dependent secretion of renal kallikrein in sliced kidney cortex and in vivo in rats. In vehicle-treated normal Brown- Norway-Kitasato (nBN-Ki) rats, the administration of glibenclamide increased urinary kallikrein secretion, but changed neither the systolic blood pressure nor the urinary sodium on low (0.3%) NaCl diets. Although on high (8%) NaCl diets, the systolic blood pressure of the nBN-Ki rats administrated glibenclamide was significantly lower (P<0.05). The urinary levels of kallikrein and sodium of the nBN-Ki rats administrated glibenclamide were significantly increased (P<0.05, glibenclamide vs. vehicle). A similar result was obtained with a kidney-selective ATP-sensitive potassium blocker, N,N'-dicyclohexyl-4-morpholinecarboxamidine (U18177), in SD rats. Mutant kininogen-deficient Brown-Norway Katholiek (muBN-Ka) rats fed high (8%) NaCl diets showed an increase in urinary kallikrein levels, but showed neither hypotensive nor natriuretic actions by glibenclamide. A bradykinin B(2) receptor antagonist, 8-[3-[N-(E)-3-(6-acetamidopyridin-3-yl) acryloylglyycyl]-N-methylamino]-2,6-dichlorobenzyloxy]-2-methylquinoline (FR173657), which was administrated to SD rats, together with glibenclamide, abolished the hypotensive and natriuretic effects of glibenclamide in high-sodium (8%NaCl) hypertension, despite an accelerated secretion of urinary kallikrein. Therefore, these results indicate that glibenclamide, an ATP-sensitive potassium channel blocker suppressed sodium-induced hypertension through sodium excretion from the kidney resulting from accelerated secretion of urinary kallikrein.
Kamata
Yuji
Y
Department of Endocrinology, Diabetes and Metabolism, Kitasato University, School of Medicine, Sagamihara, Kanagawa, Japan.
Fujita
Tomoe
T
Kato
Tetsuki
T
Hayashi
Izumi
I
Kurosaka
Maya
M
Katori
Makoto
M
Fujita
Yoshikuni
Y
Majima
Masataka
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003404:Creatinine / Q000652:urine; D004912:Erythrocytes / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced* / Q000517:prevention & control* / Q000652:urine; D007004:Hypoglycemic Agents / Q000494:pharmacology; D054086:KATP Channels / Q000037:antagonists & inhibitors*; D007610:Kallikreins / Q000652:urine*; D007704:Kininogens / Q000172:deficiency / Q000235:genetics; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000037:antagonists & inhibitors* / Q000097:blood / Q000652:urine
D000894:Anti-Inflammatory Agents, Non-Steroidal; C105311:FR 173657; D007004:Hypoglycemic Agents; D054086:KATP Channels; D007704:Kininogens; D009025:Morpholines; D026902:Potassium Channel Blockers; D011804:Quinolines; C090435:N,N'-dicyclohexyl-4-morpholinecarboxamidine; D012964:Sodium; D003404:Creatinine; D007610:Kallikreins; D005905:Glyburide