Effect of quercetin on altered vascular reactivity in aortas isolated from streptozotocin-induced diabetic rats

Abstract

The present work examined ex vivo the acute effect of quercetin on diabetic rat aortic ring reactivity in response to endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) relaxants, and to the alpha(1)-adrenergic agonist phenylephrine (PE). Responses were compared to those of aortic rings from age- and sex-matched euglycemic rats. Compared to euglycemic rat aortic rings, diabetic rings showed less relaxation in response to ACh and SNP, and greater contraction in response to PE. Pretreatment with quercetin (10microM, 20min) increased ACh-induced relaxation and decreased PE-induced contraction in diabetic, but did not affect euglycemic rat aortic ring responses. Following pretreatment with the nitric oxide synthase inhibitor Nomega-nitro-l-arginine methyl ester (l-NAME, 10microM), quercetin reduced PE-induced contractions in both aortic ring types, although l-NAME attenuated the reduction in the diabetic rings. Quercetin did not alter SNP vasodilatory effects in either ring type compared to their respective controls. These findings indicate that quercetin acutely improved vascular responsiveness in blood vessels from diabetic rats, and that these effects were mediated, at least in part, by enhanced endothelial nitric oxide bioavailability. These effects of quercetin suggest the possible beneficial effects of quercetin in vivo in experimental diabetes and possibly in other cardiovascular diseases.

Role of oxidative stress in elevated blood pressure induced by high free fatty acids

“…[25][26][27] In brief, the rats were anesthetized with pentobarbital (60 mg per kg body weight, i.p. ), the descending thoracic aorta was dissected, cut into small rings (3-5 mm in width), and suspended in a 5-ml organ bath containing normal Krebs physiological salt solution.…”

Biphasic effect of Psidium guajava Linn. (Myrtaceae) leaf aqueous extract on rat isolated vascular smooth muscles

“…However, in a chronic study by Duarte et al (2001), quercetin restored endothelium-dependent relaxation. Studies by Duarte et al (2001) and Ajay et al (2006), suggest that the effects of quercetin are more pronounced when bioavailability of endothelium-derived nitric oxide (EDNO) is impaired. Flavonoids have recently been reported to elicit endothelium-derived hyperpolarizing factor (EDHF)-mediated vascular reactivity in vascular preparations (De Moura et al, 2004;Woodman and Boujaoude, 2004).…”

“…Recent available data suggest that the vascular beneficial effects of flavonoids are closely related to their free radical scavenging and antioxidant properties, which might thus protect NO from superoxide-induced inactivation (Rice-Evans and Packer, 1998; Ajay et al, 2006). Quercetin is a potent antioxidant, and has been shown to protect nitric oxide from scavenging actions of superoxide anion (Ajay et al, 2006). In some reports, the vasorelaxation induced by quercetin (and other related flavonoids) was endothelium-independent (Duarte et al, 1993a, Perez-Vizcaíno et al, 2002, or very weakly (less than 2-fold shift) inhibited by endothelial removal (Chen and Pace-Asciak, 1996).…”

“…The vasorelaxant effect of Psidium guajava leaf aqueous extract was found to be smaller in endothelium-denuded aortic ring preparations, suggesting that PGE-induced vasodilation might be mediated, at least in part, through EDRF mechanisms. Acute activation of endothelial nitric oxide synthase (eNOS) by ACh results in the synthesis and/or release of endothelial nitric oxide (NO), which in turn leads to guanylate cyclase activation, cyclic guanosine monophosphate (cGMP) elevation, leading ultimately to vascular smooth muscle relaxation (Ajay et al, 2006). Recent available data suggest that the vascular beneficial effects of flavonoids are closely related to their free radical scavenging and antioxidant properties, which might thus protect NO from superoxide-induced inactivation (Rice-Evans and Packer, 1998; Ajay et al, 2006).…”

“…Acute activation of endothelial nitric oxide synthase (eNOS) by ACh results in the synthesis and/or release of endothelial nitric oxide (NO), which in turn leads to guanylate cyclase activation, cyclic guanosine monophosphate (cGMP) elevation, leading ultimately to vascular smooth muscle relaxation (Ajay et al, 2006). Recent available data suggest that the vascular beneficial effects of flavonoids are closely related to their free radical scavenging and antioxidant properties, which might thus protect NO from superoxide-induced inactivation (Rice-Evans and Packer, 1998; Ajay et al, 2006). Quercetin is a potent antioxidant, and has been shown to protect nitric oxide from scavenging actions of superoxide anion (Ajay et al, 2006).…”