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High‐salt diet increases endogenous carbon monoxide production to promote hypertension in Dahl salt‐sensitive rats
Author(s) -
Johnson Robert A,
Jackson Keith E,
Peyton Kelly J,
Durante William,
Johnson Fruzsina K
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a306-c
Subject(s) - excretion , nitric oxide , blood pressure , medicine , endocrinology , chemistry , endogeny
Heme oxygenase (HO) converts heme to form carbon monoxide (CO). HO‐derived CO inhibits nitric oxide synthase and promotes endothelial dysfunction in Dahl salt‐sensitive (Dahl‐S) rats with salt‐induced hypertension. Dietary zinc is known to promote endogenous formation of a HO inhibitor, zinc protoporphyrin. This study tests the hypothesis that zinc can be used to limit HO‐derived CO formation and confer protection against hypertension in Dahl‐S rats on high‐salt (HS) diets. Male Dahl‐S rats were placed on low (0.3% NaCl, LS) or HS (8% NaCl) diets and received 90mg/kg/day ZnCl 2 or vehicle in the drinking water. Respiratory CO excretion and blood pressure were measured weekly in conscious rats via solid‐phase gas chromatography and tail‐cuff plethysmography. CO excretion (HS: Δ+0.57±0.07 μmol/hr per kg) andsystolic blood pressure (HS: 132±4 to 251±5 mmHg) increased markedly in HS rats. ZnCl 2 treatment attenuated the HS diet induced increase in respiratory CO excretion (Δ+0.11±0.14 μmol/hr per kg) and blood pressure (132±9 to 181±19 mmHg), and increased plasma NOx (39%). These data show that HS diet increases blood pressure and endogenous CO formation in Dahl‐S rats, and that ZnCl 2 can be used to normalize CO formation, increase nitric oxide synthesis and restore normal blood pressure. Supported by NIH/NCRR grant P20 RR017659 (FKJ), NIH/NHLBI RO1 grants HL76187 (RAJ), HL59976 (WD) and HL74966 (WD).