OR-57: In the stroke-prone spontaneously hypertensive rat (SHRSP) the chloride component of KCl induces stroke by exacerbating hypertension

In the stroke-prone spontaneously hypertensive rat (SHRSP) we tested this hypothesis: Dietary chloride, not dietary potassium or sodium, is the dominant electrolytic determinant of phenotypic expression. We studied 98 SHRSP in which blood pressure (BP) was measured radio-telemetrically, directly and continually. In 52 rats fed a low-normal NaCl diet (0.4%), supplementing dietary potassium with KCl (n=17) exacerbated hypertension and renal microangiopathy and induced strokes in half, whereas supplementing KHCO3 (n=15) attenuated hypertension and nephropathy, relative to a control group with no potassium supplementation (n=20), and induced no strokes. Plasma renin activity (PRA) was higher with KCl than with KHCO3. In 46 rats loaded with NaCl (2.6%), supplemental KCl (n=15) but not KHCO3 (n=15) exacerbated hypertension and renal microangiopathy and induced strokes in half. Strokes did not occur in a control group with no potassium supplementation (n=16). For all groups combined the average rate of rise in BP varied directly and linearly with both the average urinary excretion (R2=0.995, p=0.00016) and the dietary intake of chloride (R2=0.992, p=0.00028) but not with the urinary excretion (R2=0.442, p=0.221) or the dietary intake of sodium (R2=0.412, p=0.243), the urinary Na+/K+ ratio (R2=0.0169, p=0.835) or the dietary Na+/K+ ratio (R2=0.0019, p=0.687). With or without NaCl-loading, and for all groups combined, final BP varied directly and linearly with log PRA. Strokes occurred only in those rats in the highest quartile of BP. These data provide strong evidence that in the SHRSP dietary chloride is the dominant electrolytic determinant of phenotypic expression, even when supplemented as KCl, and that KCl induces strokes by exacerbating hypertension and possibly by inducing hyperreninemia (see Figure).