Abstract
This study analysed and compared the effects of chronic oral treatment with quercetin
or verapamil on systolic blood pressure and vascular function in deoxycorticosterone
acetate (DOCA)-salt hypertensive rats. Quercetin and verapamil inhibited the development
of DOCA-salt-induced hypertension in a similar manner. DOCA-salt-hypertensive rats
showed potassium depletion and oxidative stress, prevented only by concomitant quercetin
administration. Quercetin and verapamil treatments reduced the endothelium-independent
hyper-reactivity to KCl observed in the aorta of DOCA-salt-hypertensive rats, but
only quercetin increased the contractile responses to angiotensin II, improved endothelial
dysfunction and restored basal aortic Cu/Zn SOD expression, altered in DOCA-salt-treated
rats. In conclusion, quercetin and verapamil show similar antihypertensive effects
in mineralocorticoid hypertension, but quercetin was superior to verapamil in improving
endothelial-dependent aortic dilatation, suggesting a better vascular protection in
this volume expansion hypertension model.
Key words
Quercetin - verapamil - mineralocorticoid hypertension - antioxidant - vascular reactivity
- endothelial dysfunction
References
1
Middleton E, Kandaswami C, Theoharides T C.
The effects of plant flavonoids on mammalian cells: Implications for inflammation,
heart disease, and cancer.
Pharmacol Rev.
2000;
52
673-751
2
Hertog M GL, Feskens E JM, Hollman P CH, Katan M B, Kromhout D.
Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly
Study.
Lancet.
1993;
342
1007-11
3
Yochum L, Kushi L H, Meyer K, Folsom A R.
Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women.
Am J Epidemiol.
1999;
149
943-9
4
Gryglewski R J, Korbut R, Robak J, Swies J.
On the mechanism of antithrombotic action of flavonoids.
Biochem Pharmacol.
1987;
36
317-22
5
Duarte J, Pérez-Vizcaíno F, Zarzuelo A, Jiménez J, Tamargo J.
Vasodilator effects of quercetin in isolated rat vascular smooth muscle.
Eur J Pharmacol.
1993;
239
1-7
6
Duarte J, Pérez-Palencia R, Vargas F, Ocete M A, Pérez-Vizcaíno F, Zarzuelo A. et
al .
Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive
rats.
Br J Pharmacol.
2001;
133
117-24
7
Duarte J, Galisteo M, Ocete M A, Pérez-Vizcaíno F, Zarzuelo A, Tamargo J.
Effects of chronic quercetin treatment on hepatic oxidative status of spontaneously
hypertensive rats.
Mol Cell Biochem.
2001;
221
155-60
8
Duarte J, Jiménez R, O’Valle F, Galisteo M, Pérez-Palencia R, Vargas F. et al .
Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats.
J Hypertens.
2002;
20
1843-54
9
Hollenberg N K, Coletti C, Passan D.
Hypertension, volume and vasoconstriction: studies on the renal blood supply in SHR,
WKY and DOCA-salt rat models.
Hypertens Res.
1992;
15
3-11
10
Somers M J, Mavromatis K, Galis Z S, Harrison D G.
Vascular superoxide production and vasomotor function in hypertension induced by deoxycorticosterone
acetate-salt.
Circulation.
2000;
101
1722-8
11
Beswick R A, Zhang H, Marable D, Catravas J D, Hill W D, Webb R C.
Long-term antioxidant administration attenuates mineralocorticoid hypertension and
renal inflammatory response.
Hypertension.
2001;
37
781-6
12
Frochlich E, Apstein C, Chobanian A, Devereux R, Dustan H, Dzau V. et al .
The heart in hypertension.
N Engl J Med.
1993;
327
998-1008
13
Wangensteen R, O’Valle F, Del Moral R G, Vargas F, Osuna A.
Chronic α1-adrenergic blockade improves hypertension and renal injury in L -NAME and low-renin L -NAME-DOCA hypertensive rats.
Med Sci Monit.
2002;
8
378-84
14
Longhurst P A, Rice P J, Taylor D A, Fleming W W.
Sensitivity of caudal arteries and the mesenteric vascular bed to norepinephrine in
DOCA-salt hypertension.
Hypertension.
1988;
12
133-42
15
Counture R, Regoli D.
Vascular reactivity to angiotensin and noradrenaline in rats maintained on sodium
free or made hypertensive with deoxycorticosterone acetate and salt (DOCA/salt).
Clin Exp Hypertens.
1980;
2
25-43
16
White R M, Rivera C O, Davison C B.
Differential contribution of endothelial function to vascular reactivity in conduit
and resistance arteries from deoxycorticosterone-salt hypertensive rats.
Hypertension.
1996;
27
1245-53
17
Storm D S, Webb R C.
α-adrenergic receptors and 45 Ca2+ efflux in arteries from deoxycorticosterone acetate hypertensive rats.
Hypertension.
1992;
19
734-8
18
Molero M M, Giulumian A D, Reddy V B, Ludwig L M, Pollock J S, Pollock D M,. et al
.
Decreased endothelin binding and [Ca2+ ]i signaling in microvessels of DOCA-salt hypertensive rats.
J Hypertens.
2002;
20
1799-805
19
Linas S L, Marzec-Calvert R, Ullian M E.
K depletion alters angiotensin II receptor expression in vascular smooth muscle cells.
Am J Physiol.
1990;
258
C849-54
20
Álvarez G, Osuna A, Wangensteen R, Vargas F.
Interaction between nitric oxide and mineralocorticoids in the long-term control of
blood pressure.
Hypertension.
2000;
35
752-7
21
Mian K B, Martin W.
Differential sensitivity of basal and acetylcholine-stimulated activity of nitric
oxide to destruction by superoxide anion in rat aorta.
Br J Pharmacol.
1995;
115
993-1000
J. Duarte
Dept. Farmacología
Fac. Farmacia
Universidad de Granada
18071 Granada
Spain
Phone: +34-958-243-889
Fax: +34-958-248-964
Email: jmduarte@ugr.es