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We assessed components of lenticular short-circuit current in adult hypertensive Dahl salt-sensitive rats (DS) during chronic control (0.4% sodium) versus high (3% sodium) dietary NaCl intake begun at the age of 4 weeks until rats were studied. We also evaluated the influence of barium, a potassium channel blocker, and ouabain, a specific inhibitor of Na+, K(+)-ATPase activity, by adding them to the anterior lens surface, thus measuring barium-sensitive, ouabain-sensitive, and barium- and ouabain-in-sensitive short-circuit currents. During control NaCl intake, short-circuit current in DS and their control group, Dahl salt-resistant rats (DR), did not differ significantly. DS were subclassified into cataract-prone rats and rats unlikely to develop cataracts on the basis of their initial pressor response to the change from a normal to high NaCl diet during the first weeks of age. Although only transparent lenses were studied, total lens short-circuit current was already markedly decreased in the cataract-prone subgroup compared with DS unlikely to develop cataracts and control DR. This was in sharp contrast to the increase in short-circuit current previously reported in Sprague-Dawley rats and now observed in control DR in response to high dietary NaCl. The decrease in lens short-circuit current in cataract-prone rats was associated with lower absolute values of barium- and ouabain-sensitive short-circuit currents as well as with low barium- and ouabain-insensitive short-circuit current. Although the barium- and ouabain-sensitive components of the short-circuit current were similar in DS unlikely to develop cataracts and DR, the barium- and ouabain-insensitive component of the short-circuit current was lower in DS unlikely to develop cataracts than values in DR. Interestingly, this component of lens short-circuit current also increased in DR during chronic high NaCl, whereas the opposite change occurred in cataract-prone DS and DS unlikely to develop cataracts. Thus, the barium- and ouabain-insensitive short-circuit current may be a mechanism that protects the normal lens from developing cataracts. Possible candidates for this short-circuit current component are voltage-dependent potassium channels, calcium-activated potassium channels, or both. Our studies show altered lens short-circuit current in response to high NaCl intake in cataract-prone DS and suggest the possibility of altered lens potassium transport during sustained hypertension but before loss of lens transparency.

Our earlier studies of cataracts in Dahl salt-sensitive (DS) rats suggested the possibility of altered lens ion transport as a contributing factor in cataractogenesis in this genetic model. We also observed that those weanling DS rats with the greatest pressor response to a high salt diet eventually developed cataracts, and that changes in salt intake modified cataract formation. In the present studies, we measured lens 86Rb uptake as an index of sodium-potassium adenosine triphosphatase [(Na+,K+)-ATPase] activity in weanling DS rats before the development of cataracts or sustained hypertension. Additionally, plasma renin activity was measured to indirectly assess our hypothesis that the difference between cataract-prone DS rats and DS rats unlikely to develop cataracts might be a difference in degree of salt sensitivity. At the age of 4 weeks, 50 DS and 25 salt-resistant (DR) rats were given a high sodium diet for 2 weeks, at which time the rats were divided into three groups based on the systolic blood pressure response, that is, cataract-prone DS rats with systolic blood pressure equal to or greater than 155 mm Hg, DS rats unlikely to develop cataracts with systolic blood pressure less than or equal to 125 mm Hg, and DR rats. Lens and aqueous humor Na+ and K+, lens dry weight, and water content were not significantly different among the three groups of weanling rats. Plasma renin activity was lowest in cataract-prone DS rats and low in DS rats unlikely to develop cataracts when compared with values in DR rats.(ABSTRACT TRUNCATED AT 250 WORDS)

We have previously reported a high incidence of cataract formation in adult hypertensive salt-sensitive rats, suggesting that hypertension may be an important cataractogenic risk factor. Weanling salt-sensitive rats that eventually developed cataracts showed a marked increase in the pressor response to a high-sodium diet compared to salt-sensitive rats that did not develop cataracts. A lens and aqueous fluid electrolyte imbalance occurred in all adult salt-sensitive rats examined, but was greater in the salt-sensitive rats that developed cataracts, suggesting an alteration in lens and/or ciliary ion transport in cataracts associated with hypertension. In the present study, lens 86Rb uptake was measured in adult hypertensive salt-sensitive rats prior to cataract formation. 'Cataract-prone' salt-sensitive hypertensive rats (increased pressor response to a high sodium diet given at weanling age), salt-sensitive hypertensive rats unlikely to develop cataracts and control salt-resistant rats were studied at the age of 16 weeks. Total and ouabain-insensitive lens 86Rb uptake were measured for the determination of ouabain-sensitive uptake, an index of Na+,K+-ATPase activity. Lens ouabain-sensitive 86Rb uptake was low in adult hypertensive cataract-prone salt-sensitive rats before cataract formation compared with values in control resistant rats. Intermediate values were observed in hypertensive salt-sensitive rats unlikely to develop cataracts. These data suggest that altered ion transport may play a pivotal role in cataractogenesis associated with this model of hypertension. The data are also consistent with the concept of a generalized defect in epithelial ion transport, at least in salt-sensitive hypertension.