Genetically determined chloride-sensitive hypertension and stroke

The stroke-prone spontaneously hypertensive rat (SHRSP) is a genetically determined model of “salt-sensitive” stroke and hypertension whose full phenotypic expression is said to require a diet high in Na(+) and low in K(+). We tested the hypothesis that dietary Cl(−) determines the phenotypic expression of the SHRSP. In the SHRSP fed a normal NaCl diet, supplementing dietary K(+) with KCl exacerbated hypertension, whereas supplementing either KHCO(3) or potassium citrate (KB/C) attenuated hypertension, when blood pressure (BP) was measured radiotelemetrically, directly and continually. Supplemental KCl, but not KB/C, induced strokes, which occurred in all and only those rats in the highest quartiles of both BP and plasma renin activity (PRA). PRA was higher with KCl than with KB/C. These observations demonstrate that with respect to both severity of hypertension and frequency of stroke the phenotypic expression of the SHRSP is (i) either increased or decreased, depending on whether the anionic component of the potassium salt supplemented is, or is not, Cl(−); (ii) increased by supplementing Cl(−) without supplementing Na(+), and despite supplementing K(+); and hence (iii) both selectively Cl(−)-sensitive and Cl(−)-determined. The observations suggest that in the SHRSP selectively supplemented with Cl(−) the likelihood of stroke depends on the extent to which both BP and PRA increase.