Selective chloride loading is pressor in the stroke-prone spontaneously hypertensive rat despite hydrochlorothiazide-induced natriuresis

Abstract

To test the hypothesis that in the stroke-prone spontaneously hypertensive rat (SHRSP), the pressor effect of selective dietary chloride loading depends on a positive external sodium balance. In 43 male SHRSP fed a Japanese style diet containing a low normal amount of NaCl (0.4%), we compared the effects on telemetrically measured SBP of hydrochlorothiazide, 25 mg/kg per day, alone ('TZ', n = 11); hydrochlorothiazide combined with either KCl ('KCLTZ', 2%K, n = 10) or KHCO3 ('KBCTZ', 2%K, n = 11) and no hydrochlorothiazide ('CTL', n = 11) over a 10-week period starting at 10 weeks of age. With either TZ or KBCTZ, SBP did not increase above baseline values. However, KCLTZ induced a sustained increase in SBP of 17 mmHg (P < 0.0001), an increase almost half of that occurring without hydrochlorothiazide (CTL), 38 mmHg (P < 0.0001). Such divergence of blood pressures with KCLTZ and KBCTZ began over the first 3 days of their administration, even while they induced similarly negative external sodium balances, a positive one occurring only in CTL. Body weight increased more without, than with, hydrochlorothiazide, but did not differ between KCLTZ and KBCTZ. Changes in SBP occurring on day 2 after treatment assignment predicted final changes. These results demonstrate that in the SHRSP, dietary KCl loading can induce a pressor effect despite concomitant hydrochlorothiazide-induced natriuresis that elicits a negative external sodium balance. The results provide evidence that in the SHRSP the pressor effect of selective chloride loading does not depend on a positive external sodium balance, but rather on a mechanism actuated by chloride per se.