Chloride-dominant salt sensitivity in the stroke-prone spontaneously hypertensive rat.
We tested the hypothesis that in the stroke-prone spontaneously hypertensive rat (SHRSP), the Cl- component of dietary NaCl dominantly determines its pressor effect (salt-sensitivity). We telemetrically measured systolic aortic blood pressure (SBP) in SHRSP loaded with: nothing (CTL); NaCl alone (NaCl) (44 mmol/100 grams chow); KCl (KCl) alone (44 mmol); NaCl (44 mmol) combined with KHCO3 (77 mmol) (NaCl/KBC) or with KCl (77 mmol) (NaCl/KCl). Across all groups, from age 10 to 15 or 16 weeks, SBP increased linearly (mm Hg/week) (dp/dt, change in SBP as a function of time): CTL, 5.6; NaCl, 9.5; KCl, 8.8; NaCl/KBC, 9.1; and NaCl/KCl, 14.6. Thus, the value of dp/dt in KCl matched that in NaCl. The value of dp/dt in NaCl/KCl exceeded that in NaCl in direct proportion to the greater Cl- load. Across all groups, only Cl- load bore a direct, highly linear relationship with dp/dt. Strokes occurred only, but always with SBP >250 mm Hg, a value observed almost exclusively in NaCl/KCl. Thus, Cl- dominantly determined the pressor effect induced with dietary NaCl, both with NaCl loaded alone and combined with either KCl or KHCO3, and thereby likely determined the occurrence of stroke with NaCl loading. Over the initial 3-day period of NaCl loading and exacerbating hypertension, external balance of Na+ increased similarly among all groups. However, within 24 hours of initiating NaCl loading, urinary creatinine excretion decreased in direct proportion to dp/dt and urinary Cl- excretion. We conclude that in the SHRSP, the Cl- component of a dietary NaCl dominantly determines salt sensitivity and thereby phenotypic expression. We suggest that Cl- might do so by inducing renal vasoconstriction.
Schmidlin
Olga
O
Department of Medicine, Division of Nephrology, University of California at San Francisco, CA 94143-0126, USA.
Tanaka
Masae
M
Bollen
Andrew W
AW
Yi
Sai-Li
SL
Morris
R Curtis
RC
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002712:Chlorides / Q000652:urine; D003404:Creatinine / Q000652:urine; D004338:Drug Combinations; D004573:Electrolytes / Q000652:urine; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000139:chemically induced* / Q000652:urine; D015994:Incidence; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D017680:Potassium Compounds / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D012965:Sodium Chloride / Q000494:pharmacology; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*
D001639:Bicarbonates; D002712:Chlorides; D004338:Drug Combinations; D004573:Electrolytes; D017680:Potassium Compounds; D012965:Sodium Chloride; D011189:Potassium Chloride; D003404:Creatinine; C026329:potassium bicarbonate