An alternative hypothesis to the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension.

It is widely held that in response to high salt diets, normal individuals are acutely and chronically resistant to salt-induced hypertension because they rapidly excrete salt and retain little of it so that their blood volume, and therefore blood pressure, does not increase. Conversely, it is also widely held that salt-sensitive individuals develop salt-induced hypertension because of an impaired renal capacity to excrete salt that causes greater salt retention and blood volume expansion than that which occurs in normal salt-resistant individuals. Here we review results of both acute and chronic salt-loading studies that have compared salt-induced changes in sodium retention and blood volume between normal subjects (salt-resistant normotensive control subjects) and salt-sensitive subjects. The results of properly controlled studies strongly support an alternative view: during acute or chronic increases in salt intake, normal salt-resistant subjects undergo substantial salt retention and do not excrete salt more rapidly, retain less sodium, or undergo lesser blood volume expansion than do salt-sensitive subjects. These observations: (i) directly conflict with the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension, and (ii) have implications for contemporary understanding of how various genetic, immunologic, and other factors determine acute and chronic blood pressure responses to high salt diets.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Chloride-dominant salt sensitivity in the stroke-prone spontaneously hypertensive rat.

We tested the hypothesis that in the stroke-prone spontaneously hypertensive rat (SHRSP), the Cl- component of dietary NaCl dominantly determines its pressor effect (salt-sensitivity). We telemetrically measured systolic aortic blood pressure (SBP) in SHRSP loaded with: nothing (CTL); NaCl alone (NaCl) (44 mmol/100 grams chow); KCl (KCl) alone (44 mmol); NaCl (44 mmol) combined with KHCO3 (77 mmol) (NaCl/KBC) or with KCl (77 mmol) (NaCl/KCl). Across all groups, from age 10 to 15 or 16 weeks, SBP increased linearly (mm Hg/week) (dp/dt, change in SBP as a function of time): CTL, 5.6; NaCl, 9.5; KCl, 8.8; NaCl/KBC, 9.1; and NaCl/KCl, 14.6. Thus, the value of dp/dt in KCl matched that in NaCl. The value of dp/dt in NaCl/KCl exceeded that in NaCl in direct proportion to the greater Cl- load. Across all groups, only Cl- load bore a direct, highly linear relationship with dp/dt. Strokes occurred only, but always with SBP >250 mm Hg, a value observed almost exclusively in NaCl/KCl. Thus, Cl- dominantly determined the pressor effect induced with dietary NaCl, both with NaCl loaded alone and combined with either KCl or KHCO3, and thereby likely determined the occurrence of stroke with NaCl loading. Over the initial 3-day period of NaCl loading and exacerbating hypertension, external balance of Na+ increased similarly among all groups. However, within 24 hours of initiating NaCl loading, urinary creatinine excretion decreased in direct proportion to dp/dt and urinary Cl- excretion. We conclude that in the SHRSP, the Cl- component of a dietary NaCl dominantly determines salt sensitivity and thereby phenotypic expression. We suggest that Cl- might do so by inducing renal vasoconstriction.