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 pl asma renin activity (PRA) to systemic application of U37883A midine-N- 1-adamantyl-N'-cyclohexyl-hydrochloride), a putative blocker of ATP-se nsitive potassium channels (K-ATP), and P1075 (N-cyano-N'-(1,1-dimethy lpropyl)-N ''-pyridylguanidine), an opener of K-ATP channels, was stud ied 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 (U V) 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 mu g/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 incr eased by P1075. Variation in potassium diet (0.04 or 2% K) left the re sponse in MAP, HR or GFR to both potassium channel modulators essentia lly unchanged. The reduction in renal excretion rates to P1075 also ap peared 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 pota ssium diet U37883A did no longer cause a significant natriuresis; (2) U37883A elicited a significant kaliuresis under high potassium diet, w hereas 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 evid ence that P1075 releases renin from freshly isolated juxtaglomerular c ells of rats on normal but not on low potassium diet. In summary, syst emic potassium channel modulation employing U37883A or P1075, respecti vely, exerts distinct effects on blood pressure and heart rate indepen dent of potassium diet. In contrast, potassium diet appears to be a de terminant for the concomitant reponses in plasma renin activity and re nal sodium and potassium excretion.