Defect of the Potassium Transport Process in the Kidney of Spontaneously Hypertensive Rats

Abstract

We investigated the natriuretic and kaliuretic effect of distal tubular diuretics in saline-loaded spontaneously hypertensive Wistar rats (SHR) from three different sources and normotensive Wistar rats (NWR). Orally administered early distal tubular diuretics (hydrochlorothiazide, chlorthalidone, metolazone, indapamide and cicletanine) caused much less potassium excretion in SHR than in NWR, whereas the magnitude of concurrent natriuresis was similar in both NWR and SHR. The intriguing renal handling of potassium excretion was exemplified by hydrochlorothiazide, for which enhanced kaliuresis was dose dependent in NWR but not in SHR. The doses tested ranged from 1 to 100 mg/kg, p.o. Amiloride, a late distal tubular diuretic, was also evaluated for its effect on sodium and potassium excretion in NWR and SHR. Amiloride produced potassium retention more effectively in NWR than in SHR, although the magnitude of natriuresis was similar. The difference between SHR and NWR with regard to potassium-retaining activity of amiloride was consistent at all doses tested (1-30 mg/kg, p.o.). In conclusion, it was suggested that SHR appear to have a genetic defect in potassium transport in the distal nephron.

Sodium transport antagonism reduces thrombotic microangiopathy in stroke-prone spontaneously hypertensive rats

“…These animals were also maintained on a high-sodium intake, and sodium has been shown to interfere with the ability of amiloride to inhibit sodium conductance in vitro (3). Furthermore, amiloride has been reported to produce less potassium retention in SHR, the progenitor strain of SHRSP, than in normotensive Wistar rats (19). The absence of a hyperkalemic response is probably due to a combination of reduced potassium intake, increased sodium intake, and a genetic defect in potassium transport in the distal nephron of these rats.…”

Pharmacodynamic effects of the K + binder patiromer in a novel chronic hyperkalemia model in spontaneously hypertensive rats

“…Moreover, the SHR model is a well-established disease model and follows similar progression as human HTN, with pre-, developing, and sustained periods of hypertensive phases (Doggrell & Brown, 1998). One very important feature of SHRs is that renal K + handling is inherently compromised in this rat strain-possibly due to a genetic defect in the K + transport in the distal nephron (Kau, Pritchard, & Leszczynska, 1992). We also chose the SHR model for the propensity of the animals to develop several renal defects that mimicked the pathological process of CKD, which is a key underlying comorbidity in patients who develop HK, in addition to those mentioned above.…”