Effects of valsartan and 17 beta-estradiol on the oxidation of low-density lipoprotein in vitro.
BACKGROUND
The 'sartans' are antagonists of the angiotensin type 1 (AT1) receptor that are mainly used for treatment of hypertension. Little is known about AT1-independent effects of these substances and interactions with other drugs used for prevention of cardiovascular diseases. Postmenopausal estradiol-replacement therapy has been shown to exert beneficial antiathero-sclerotic properties by inhibiting oxidation of low-density lipoprotein (LDL).


OBJECTIVE
In the present study, the effects of valsartan alone and in combination with 17 beta-estradiol on the oxidation of isolated human LDL were investigated.


METHODS
Oxidation of LDL, which was triggered by copper (II) chloride, was monitored spectrometrically at 234 nm. The test substances were added in vitro.


RESULTS
Valsartan alone increased the duration of resistance of LDL to oxidation by 75.3 +/- 5.7 min at 5 mumol/l and by 138.2 +/- 8.1 min at 10 mumol/l. 17 beta-estradiol alone delayed the onset of oxidation of LDL by 75.7 +/- 5.1 min at 1 mumol/l. With the combination of 5 and 10 mumol/l valsartan with 1 mumol/l estradiol the time to onset of oxidation of LDL was increased by 142.8 +/- 4.9 and 215.3 +/- 6.9 min, respectively.


CONCLUSIONS
There has been demonstrated an antioxidative effect of valsartan that was additive to that of 17 beta-estradiol. Thus this combination has the potential to be useful in the treatment of postmenopausal women with hypertension.
Seeger
H
H
Department OB/GYN, University of Tübingen, Germany.
Mueck
A O
AO
Lippert
T H
TH
D000959:Antihypertensive Agents / Q000494:pharmacology*; D008078:Cholesterol, LDL / Q000378:metabolism*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D017698:Postmenopause; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D000959:Antihypertensive Agents; D008078:Cholesterol, LDL; D013777:Tetrazoles; D004958:Estradiol; D000068756:Valsartan; D014633:Valine