Early increases in renal kallikrein secretion on administration of potassium or ATP‐sensitive potassium channel blockers in rats

• Published in: British journal of pharmacology Vol. 128; no. 6; pp. 1275 - 1283
• Main Authors: Fujita, Tomoe, Hayashi, Izumi, Kumagai, Yuji, Inamura, Naoya, Majima, Masataka
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.1999; Nature Publishing
• Subjects: Adamantane - analogs & derivatives; Adamantane - pharmacology; Adenosine Triphosphate - physiology; Animals; ATP‐sensitive potassium channel blocker; Biological and medical sciences; Chlorides - urine; Dose-Response Relationship, Drug; Endocrine kidney. Renin-angiotensin-aldosterone system; Fundamental and applied biological sciences. Psychology; glibenclamide; Gluconates - pharmacology; Glyburide - pharmacology; In Vitro Techniques; Kallikreins - drug effects; Kallikreins - metabolism; Kallikreins - urine; Kidney - drug effects; Kidney - metabolism; Male; Morpholines - pharmacology; osmotic diuretic; Perfusion; Polyethylene Glycols - pharmacology; potassium; Potassium - pharmacology; Potassium - urine; Potassium Channel Blockers; Potassium Chloride - pharmacology; Rats; Rats, Sprague-Dawley; renal kallikrein secretion; Sodium - urine; Time Factors; Urination - drug effects; Vertebrates: endocrinology; volume load; Animal model; Intravenous administration; Rat; Potassium channel antagonist; Potassium ion; Secretion; Rodentia; Ionic channel; In vitro; Biological activity; Kidney; Tissue; Vertebrata; Mammalia; Animal; Sulfonylureas; Glibenclamide
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702899

This study aimed to examine whether administration of potassium or ATP‐sensitive potassium channel (KATP channel) blockers caused early increases in renal kallikrein (KK) secretion. To clarify this mechanism, the effect on renal KK secretion of a KATP channel blocker was compared with the effect resulting from use of an osmotic diuretic or volume load. Furthermore, the effect on potassium‐induced increases in renal KK secretion by an additional treatment using a KATP channel blocker was examined. Lastly, the effect of a KATP channel blocker on renal KK secretion was also examined in superfused slices of kidney cortex. Intravenous infusion of potassium augmented renal KK secretion within 30 min while urine volume increased gradually in both the potassium loading and control groups. Administration of the KATP channel blocker, 4‐morpholinecarboximidine‐N‐1‐adamantyl‐N′‐cyclohexylhydrochloride (PNU‐37883A) or glibenclamide, caused a dose‐dependent increase in renal KK secretion. The concentration of KK in urine was higher in the PNU‐37883A group as compared to the osmotic‐diuretic or volume‐load group. PNU‐37883A had no additive effect on the potassium‐induced increase in renal KK secretion. Renal KK secretion increased in slices of kidney cortex incubated with PNU‐37883A within 10 min of superfusion. In conclusion, administration of both potassium and KATP channel blockers induced early increases in renal KK secretion in the absence of the washout phenomenon. Potassium loading may have increased renal KK secretion through the same mechanism as the KATP channel blocker. British Journal of Pharmacology (1999) 128, 1275–1283; doi:10.1038/sj.bjp.0702899