K+ loading, but not Na+ loading, and blockade of ATP-sensitive K+ channels augment renal kallikrein secretion.
This study aimed to examine whether K+ loading or Na+ loading augments renal kallikrein (KK) secretion. It also investigated the effect of blockade of renal ATP-sensitive K+ channels on renal KK secretion. Rats were administered 50 mmol/kg body weight of KCl. Twelve-hour collected urine was measured for urinary excretion of K+ and Na+ and urinary activity of renal KK. Increases in urinary excretion of K+ and Na+ by K+ loading accompanied an increase in renal KK secretion. In another experiment, rats were infused intravenously with a solution of 75 mM K+ and 75 mM Na+, 150 mM Na+ or 300 mM Na+ for 150 min under anesthesia. Urinary KK activity was measured in urine collected every 30 min. Renal KK secretion began to increase within the 30 min infusion of K+ solution and persisted at more elevated levels during the infusion with K+ solution than with Na+ solutions. Furthermore, rats were given intravenous injection of ATP-sensitive K+ channel blocker, either PNU-37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl) at a concentration of 10 mg/kg or glibenclamide at 30 mg/kg. Renal KK secretion increased 30 min after administration of both PNU-37883A and glibenclamide. In conclusion, it may be that augmentation of renal KK secretion by K+ loading occurred through an increase in urinary K+ excretion followed by the inhibition of K+ transport from ATP-sensitive K+ channels.
Fujita
T
T
Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Hayashi
I
I
Kumagai
Y
Y
Inamura
N
N
Majima
M
M
D018528:ATP-Binding Cassette Transporters; D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels; D007610:Kallikreins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism* / Q000652:urine; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D054086:KATP Channels; D009025:Morpholines; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; C082658:U 37883A; D012964:Sodium; D007610:Kallikreins; D000218:Adamantane; D011188:Potassium; D005905:Glyburide