potassium-bicarbonate and Proteinuria

In the stroke-prone spontaneously hypertensive rat (SHRSP) fed a low-normal NaCl diet, we recently reported that supplemental KCl, but not KHCO(3) or K-citrate (KB/C), exacerbated hypertension and induced hyperreninemia and strokes. We now ask the following question: In these SHRSP, is either such selectively Cl(-)-sensitive hypertension or hyperreninemia a pathogenetic determinant of renal microvasculopathy?. SHRSPs were randomized to either supplemental KCl, KB/C, or nothing (control) at 10 weeks of age. Four and 14 weeks afterward, we assessed renal microangiopathy histologically and measured plasma renin activity (PRA). From randomization, blood pressure was measured radiotelemetrically and continually; proteinuria was measured periodically.. KCl, but not KB/C, amplified renal microangiopathy and proteinuria. Four weeks after randomization, when KCl initially exacerbated hypertension, renal microangiopathy, hyperproteinuria, and hyperreninemia had not yet occurred. However, across all groups, the increment of SBP at four weeks strongly predicted its final increment, severity of renal microangiopathy, proteinuria, and PRA 14 weeks after randomization. Then, the severity of renal microangiopathy varied directly with the levels of systolic blood pressure (SBP; R(2) = 0.9, P < 0.0001), PRA (R(2) = 0.7, P < 0.0001), and proteinuria (R(2) = 0.8, P < 0.0001) as continuous functions across all treatment groups. Renal creatinine clearance was greater with KB/C.. In the SHRSP, (1) like cerebral microangiopathy, renal microangiopathy is selectively Cl(-) sensitive and hence, systemic microangiopathy is as well; (2) Cl(-) likely amplifies microangiopathy by exacerbating hypertension and possibly also by increasing PRA; and (3) Cl(-) might increase blood pressure and PRA by further constricting the renal afferent arteriole.

Topics: Animals; Bicarbonates; Blood Pressure; Chlorides; Creatinine; Disease Susceptibility; Hypertension; Male; Microcirculation; Potassium Chloride; Potassium Citrate; Potassium Compounds; Proteinuria; Rats; Rats, Inbred SHR; Renal Circulation; Renin; Severity of Illness Index; Stroke; Vascular Diseases