Effect of quercetin on plasma extravasation in rat CNS and dura mater by ACE and NEP inhibition

Abstract

The effects of quercetin on substance P-induced plasma protein extravasation (PE) in the rat dura mater, cerebellum, olfactory bulb and cortex and also its modulation by endopeptidases, angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) were studied. PE was assessed by photometric measurement of extravasated Evans blue. Substance P (SP) and NEP or ACE inhibitors increased the PE in dura mater. Pretreatment with captopril or phosphoramidon potentiated PE induced by SP in the dura mater and cerebellum, respectively. Quercetin increased the PE in the dura mater, cerebellum and cortex. Further results suggested that the PE induced by SP in the dura mater was enhanced by pretreatment with quercetin, similar to that observed with selective peptidase inhibitors. Quercetin-stimulated extravasation in all tissues was abolished by NK-1 receptor blockade. These results suggest that quercetin increases PE in the dura mater and CNS tissues by inhibiting NEP and/or ACE, showing that the effect induced in the dura mater, cerebellum and cortex occurs through endogenous SP accumulation.

Antihypertensive properties of flavonoid-rich apple peel extract

“…This suggests that quercetin metabolites could interfere with RAAS and inhibit ACE activity in vivo. Several studies reported that quercetin can reduce plasma extravasation by inhibiting ACE and endopeptidases (Cyrino, Cardoso, Hackl, &Willie, Riberio-do-Valle, Simoes, Gabilan, &Nicalou, 2001). These results could be due to the activity of active metabolites of quercetin such as quercetin-3-O-glucuronic acid.…”

Neurokinin-1 receptor inhibition reverses ischaemic brain injury and dementia in bilateral common carotid artery occluded rats: possible mechanisms

“…An elevated level of substance P has been documented to be a major risk factor for vascular dementia. Intravenous administration of substance P to rats has been shown to cause a significant increase in plasma extravasation, an effect abolished by pretreatment with an NK1 tachykinin antagonist (Cyrino et al 2002). It has also been reported that the activation of NK1 tachykinin receptors on vascular endothelium may contribute to cerebral edema (Stumm et al 2001).…”

The Role of Substance P in Ischaemic Brain Injury

“…Consistent with an important role of SP in TBI, clinical and experimental studies have reported adverse effects of ACE [82] or NEP inhibition, the enzymes which degrade SP, as this exaggerates the effects of released SP [83]. Indeed, ACE and NEP inhibitors have been found to increase plasma extravasation [74]. …”

“…Chemical, electrical or immunological stimulation, or treatment with capsaicin, was found to elicit a neurogenic inflammatory response in the dura mater but not the pia or cerebral cortex [73]. Similarly, intravenous administration of SP to rats has been shown to cause a significant increase in plasma extravasation in the dura mater, an effect abolished by pre-treatment with an NK1 tachykinin antagonist [74]. It was previously proposed that the activation of NK1 tachykinin receptors on vascular endothelium may contribute to cerebral oedema [75].…”