The effect of losartan and losartan/hydrochlorothiazide fixed-combination on magnesium, zinc, and nitric oxide metabolism in hypertensive patients: a prospective open-label study.
BACKGROUND
Thiazide diuretics and angiotensin-converting enzyme inhibitors can cause excessive urinary zinc (Zn) loss and Zn depletion. Thiazides may also induce magnesium (Mg) deficiency, which may exacerbate hypertension. Data on the effects of angiotensin receptor blockers on Zn and Mg homeostasis are scarce.


METHODS
Seventeen hypertensive patients were studied (ten men and seven women, age 50 +/- 3 years, blood pressure 158 +/- 5 / 95 +/- 3 mm Hg). Patients were treated with losartan 50 mg/day for 4 weeks followed by a fixed combination of 50 mg losartan and 12.5 mg hydrochlorothiazide for 4 weeks more. Blood and 24-h urine were collected at baseline and after each study period. Zinc and Mg levels were measured in serum, urine, and peripheral blood mononuclear cells. Nitric oxide metabolites were measured in urine.


RESULTS
Treatment with losartan resulted in a significant increase in the urinary Zn/creatinine ratio (from 0.020 +/- 0.004 microg/mg to 0.034 +/- 0.005 microg/mg, P = .02), which was further increased by the losartan/hydrochlorothiazide combination (from 0.034 +/- 0.005 microg/mg to 0.053 +/- 0.008 microg/mg, P = .03). Serum Zn levels were significantly decreased after losartan/hydrochlorothiazide (from 80.0 +/- 4.0 microg/dL at baseline to 74.0 +/- 3.0 microg/dL, P = .007). Peripheral blood mononuclear Zn concentrations were decreased also, but this was not statistically significant. Serum, urinary, and peripheral blood mononuclear Mg levels were not significantly affected by treatment. Nitric oxide urinary metabolites were unchanged throughout the study.


CONCLUSIONS
Treatment with losartan causes an increase in urinary Zn excretion and induces Zn deficiency in patients with hypertension. The addition of hydrochlorothiazide has an additive effect. Magnesium and nitric oxide metabolism are not affected by either treatment.
Koren-Michowitz
Maya
M
Department of Medicine A, Assaf-Harofeh Medical Center, Zerifin 70300, Israel.
Dishy
Victor
V
Zaidenstein
Ronit
R
Yona
Orit
O
Berman
Sylvia
S
Weissgarten
Joshua
J
Golik
Ahuva
A
D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D019808:Losartan / Q000008:administration & dosage* / Q000009:adverse effects; D008274:Magnesium / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011446:Prospective Studies; D015032:Zinc / Q000097:blood / Q000172:deficiency* / Q000652:urine
D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D009569:Nitric Oxide; D003404:Creatinine; D008274:Magnesium; D015032:Zinc; D019808:Losartan