Potassium diet as a determinant for the renal response to systemic potassium channel modulation in anesthetized rats.
The role of potassium intake in the response of kidney function and plasma renin activity (PRA) to systemic application of U37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl-hydro chloride), a putative blocker of ATP-sensitive potassium channels (K(ATP)), and P1075 (N-cyano-N'-(1,1-dimethylpropyl)-N"-pyridylguanidine), an opener of K(ATP) channels, was studied in the anesthetized rat. It was found that under normal potassium diet (0.7% K), U37883A (15 mg/kg, i.v.) increased urinary flow rate (UV) and sodium excretion (UNaV), decreased urinary potassium excretion (UKV), and significantly diminished heart rate (HR) without affecting mean arterial blood pressure (MAP) or glomerular filtration rate (GFR). P1075 (10 microg/kg, i.v.) lowered UV, UNaV and UKV, at least in part due to the fall in MAP and GFR. PRA was diminished by U37883A and increased by P1075. Variation in potassium diet (0.04 or 2% K) left the response in MAP, HR or GFR to both potassium channel modulators essentially unchanged. The reduction in renal excretion rates to P1075 also appeared unaffected, further supporting a predominant role of the change in MAP and GFR in this response. Variation in potassium diet, however, elicited the following alterations: (1) under both low and high potassium diet U37883A did no longer cause a significant natriuresis; (2) U37883A elicited a significant kaliuresis under high potassium diet, whereas potassium excretion remained essentially unchanged on very low levels under low potassium diet; (3) the increase in PRA to P1075 was blunted under low potassium diet. Additional experiments provided evidence that P1075 releases renin from freshly isolated juxtaglomerular cells of rats on normal but not on low potassium diet. In summary, systemic potassium channel modulation employing U37883A or P1075, respectively, exerts distinct effects on blood pressure and heart rate independent of potassium diet. In contrast, potassium diet appears to be a determinant for the concomitant responses in plasma renin activity and renal sodium and potassium excretion.
Vallon
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V
Department of Pharmacology, University of Tübingen, Germany.
Kirschenmann
D
D
Brenner
I
I
Albinus
M
M
Osswald
H
H
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001826:Body Fluids / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D011188:Potassium / Q000097:blood / Q000652:urine; D015221:Potassium Channels / Q000187:drug effects; D017419:Potassium, Dietary / Q000008:administration & dosage*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000097:blood / Q000652:urine; D014665:Vasodilator Agents / Q000494:pharmacology
D004232:Diuretics; D006146:Guanidines; D009025:Morpholines; D015221:Potassium Channels; D017419:Potassium, Dietary; D011725:Pyridines; D014665:Vasodilator Agents; C082658:U 37883A; C073896:N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine; D012964:Sodium; D012083:Renin; D000218:Adamantane; D011188:Potassium