Chloride-sensitive renal microangiopathy in the stroke-prone spontaneously hypertensive rat.
BACKGROUND
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?


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Tanaka
M
M
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Schmidlin
O
O
Olson
J L
JL
Yi
S L
SL
Morris
R C
RC
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology*; D003404:Creatinine / Q000378:metabolism; D004198:Disease Susceptibility; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D019357:Potassium Citrate / Q000494:pharmacology; D017680:Potassium Compounds / Q000494:pharmacology; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012720:Severity of Illness Index; D020521:Stroke / Q000209:etiology*; D014652:Vascular Diseases / Q000503:physiopathology* / Q000652:urine
D001639:Bicarbonates; D002712:Chlorides; D017680:Potassium Compounds; D011189:Potassium Chloride; D003404:Creatinine; D012083:Renin; D019357:Potassium Citrate; C026329:potassium bicarbonate