Selective chloride loading is pressor in the stroke-prone spontaneously hypertensive rat despite hydrochlorothiazide-induced natriuresis.
OBJECTIVE
To test the hypothesis that in the stroke-prone spontaneously hypertensive rat (SHRSP), the pressor effect of selective dietary chloride loading depends on a positive external sodium balance.


METHODS
In 43 male SHRSP fed a Japanese style diet containing a low normal amount of NaCl (0.4%), we compared the effects on telemetrically measured SBP of hydrochlorothiazide, 25 mg/kg per day, alone ('TZ', n = 11); hydrochlorothiazide combined with either KCl ('KCLTZ', 2%K, n = 10) or KHCO3 ('KBCTZ', 2%K, n = 11) and no hydrochlorothiazide ('CTL', n = 11) over a 10-week period starting at 10 weeks of age.


RESULTS
With either TZ or KBCTZ, SBP did not increase above baseline values. However, KCLTZ induced a sustained increase in SBP of 17 mmHg (P < 0.0001), an increase almost half of that occurring without hydrochlorothiazide (CTL), 38 mmHg (P < 0.0001). Such divergence of blood pressures with KCLTZ and KBCTZ began over the first 3 days of their administration, even while they induced similarly negative external sodium balances, a positive one occurring only in CTL. Body weight increased more without, than with, hydrochlorothiazide, but did not differ between KCLTZ and KBCTZ. Changes in SBP occurring on day 2 after treatment assignment predicted final changes.


CONCLUSIONS
These results demonstrate that in the SHRSP, dietary KCl loading can induce a pressor effect despite concomitant hydrochlorothiazide-induced natriuresis that elicits a negative external sodium balance. The results provide evidence that in the SHRSP the pressor effect of selective chloride loading does not depend on a positive external sodium balance, but rather on a mechanism actuated by chloride per se.
Department of Medicine, Division of Nephrology, University of California San Francisco, San Francisco, California 94143-0126, USA. olga@picasso.ucsf.edu
Olga
O
Schmidlin
Masae
M
Tanaka
Anthony
A
Sebastian
R Curtis
RC
Morris
D000821:Animal Feed / Q000032:analysis; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D018660:Blood Pressure Monitoring, Ambulatory; D002712:Chlorides / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D011189:Potassium Chloride / Q000008:administration & dosage; D051381:Rats; D011918:Rats, Inbred SHR; D012964:Sodium / Q000378:metabolism; D012982:Sodium, Dietary / Q000008:administration & dosage; D013686:Telemetry; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D002712:Chlorides; D004232:Diuretics; D012982:Sodium, Dietary; D006852:Hydrochlorothiazide; D011189:Potassium Chloride; D012964:Sodium