Chloride-sensitive renal microangiopathy in the stroke-prone spontaneouslyhypertensive rat

Background. In the stroke-prone spontaneously hypertensive rat (SHRSP) fed a low-normal NaCl diet, we recently reported that supplemental KCl, but not KHCO3 or K-citrate (KB/C), exacerbated hypertension and induced hyperrenin emia and strokes. We now ask the following question: In these SHRSP, is eit her such selectively Cl--sensitive hypertension or hyperreninemia a pathoge netic determinant of renal microvasculopathy? Methods. SHRSPs were randomized to either supplemental KCl, KB/C, or nothin g (control) at 10 weeks of age. Four and 14 weeks afterward, we assessed re nal microangiopathy histologically and measured plasma renin activity (PRA) . From randomization, blood pressure was measured radiotelemetrically and c ontinually; proteinuria was measured periodically. Results. KCl, but not KB/C, amplified renal microangiopathy and proteinuria . Four weeks after randomization, when KCl initially exacerbated hypertensi on, renal microangiopathy, hyperproteinuria, and hyperreninemia had not yet occurred. However, across all groups, the increment of SEP at four weeks s trongly predicted its final increment, severity of renal microangiopathy, p roteinuria, and PRA 14 weeks after randomization. Then, the severity of ren al microangiopathy varied directly with the levels of systolic blood pressu re (SBP; R-2 = 0.9, P < 0.0001), PRA (R-2 = 0.7, P < 0.0001), and proteinur ia (R-2 = 0.8, P < 0.0001) as continuous functions across all treatment gro ups. Renal creatinine clearance was greater with KB/C. Conclusions. In the SHRSP, (1) like cerebral microangiopathy, renal microan giopathy is selectively Cl- sensitive and hence, systemic microangiopathy i s as well; (2) Cl- likely amplifies microangiopathy by exacerbating hyperte nsion and possibly also by increasing PRA; and (3) Cl- might increase blood pressure and PRA by further constricting the renal afferent arteriole.