Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice

Abstract

treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice. Am J Physiol Heart Circ Physiol 300: H1032-H1043, 2011. First published December 24, 2010; doi:10.1152/ajpheart.00410.2010.-Severe dyslipidemia and the associated oxidative stress could accelerate the age-related decline in cerebrovascular endothelial function and cerebral blood flow (CBF), leading to neuronal loss and impaired learning abilities. We hypothesized that a chronic treatment with the polyphenol catechin would prevent endothelial dysfunction, maintain CBF responses, and protect learning abilities in atherosclerotic (ATX) mice. We treated ATX (C57Bl/6-LDLR Ϫ/Ϫ hApoB ϩ/ϩ ; 3 mo old) mice with catechin (30 mg · kg Ϫ1 · day Ϫ1 ) for 3 mo, and C57Bl/6 [wild type (WT), 3 and 6 mo old] mice were used as controls. ACh-and flow-mediated dilations (FMD) were recorded in pressurized cerebral arteries. Basal CBF and increases in CBF induced by whisker stimulation were measured by optical coherence tomography and Doppler, respectively. Learning capacities were evaluated with the Morris water maze test. Compared with 6-mo-old WT mice, cerebral arteries from 6-mo-old ATX mice displayed a higher myogenic tone, lower responses to ACh and FMD, and were insensitive to NOS inhibition (P Ͻ 0.05), suggesting endothelial dysfunction. Basal and increases in CBF were lower in 6-mo-old ATX than WT mice (P Ͻ 0.05). A decline in the learning capabilities was also observed in ATX mice (P Ͻ 0.05). Catechin 1) reduced cerebral superoxide staining (P Ͻ 0.05) in ATX mice, 2) restored endothelial function by reducing myogenic tone, improving ACh-and FMD and restoring the sensitivity to nitric oxide synthase inhibition (P Ͻ 0.05), 3) increased the changes in CBF during stimulation but not basal CBF, and 4) prevented the decline in learning abilities (P Ͻ 0.05). In conclusion, catechin treatment of ATX mice prevents cerebrovascular dysfunctions and the associated decline in learning capacities. endothelial function; pressurized cerebral arteries; cerebral blood flow; morris water maze ONE OF THE PRIMARY CONCERNS in neurological sciences is the relationship between cerebral blood flow (CBF) and nerve cell survival (43). The increase in CBF produced by brain activity, or functional hyperemia, is an example of the close interaction between neurons and blood vessels (12). The neurovascular unit including neurons, astrocytes and endothelial cells, physiologically controls CBF locally during neuronal activation (4,19,26). Endothelial cells play an important role in CBF regulation by releasing many vasoactive factors such as nitric oxide (NO), prostacyclin, and thromboxane A 2 (43). Upon neuronal activation, the rise in CBF is, however, also required upstream in larger arteries to accommodate the local metabolic needs; this is partly an endothelium-dependent dilatory response to the rise in shear stress (8), but vasomotor responses via gap junctions and astrocytic factors may also contribute to the regulation of blood flow in upstream art...

Up-regulation of thromboxane A2 impairs cerebrovascular eNOS function in aging atherosclerotic mice

“…We used 3-and 12-m/o C57Bl/6 male mice (WT, 29±1 g and 46±3 g, respectively, n=20; Charles River Laboratories, St-Constant, QC, Canada) and 3-and 12-m/o atherosclerotic mice (ATX, 25±1 g and 39±2 g, respectively, n=20). ATX mice are knockout for the low density lipoprotein receptor (LDLR) and express the human apolipoprotein B-100 gene (LDLR −/− ; hApoB +/+ [6,44]). Founders of the colony were generous gifts from Dr. H. Hobbs (University of Texas Southwestern, Dallas, TX, USA).…”

“…The vessels were opened, pinned, and a picture was taken. Plaque area quantification was calculated with Photoshop software and expressed in percentage of total aortic area [6].…”

“…In addition, brain sections containing the basilar artery were processed similarly to evaluate cerebrovascular oxidative stress [6]. DNA counterstaining was performed using ToPro-3 (2 μM; Molecular Probe, Burlington, ON, Canada).…”

Isolated Human and Rat Cerebral Arteries Constrict to Increases in Flow: Role of 20-HETE and TP Receptors

“…Previous studies showed that increases in pressure elicit increases in resistance of cerebral vessels (Cipolla et al, 2002;Davis and Hill, 1999;Faraci et al, 1989;Heistad and Baumbach, 1992;Kontos, 1981;Osol et al, 2002;Wallis et al, 1996). However, vasomotor responses to increases in flow in isolated cerebral vessels varied: dilation (Drouin et al, 2011;Drouin and Thorin, 2009;Gaw and Bevan, 1993), constriction (Bryan et al, 2001a;Madden and Christman, 1999), and biphasic responses Bevan, 1990, 1991;Ngai and Winn, 1995;Shimoda et al, 1996;Shimoda et al, 1998;Thorin-Trescases and Bevan, 1998) were observed. Importantly, no data are available regarding human cerebral vessels preventing the translation of knowledge from vertebrates to humans.…”

Postnatal exposure to voluntary exercise but not the antioxidant catechin protects the vasculature after a switch to an atherogenic environment in middle-age mice

“…EX mice had free access to a running wheel (Lafayette Instrument, Lafayette, IN, USA) without reward [5] and ran an average of 2.7±0.2 km/day over the 8-month period of exposure. The polyphenol CAT was dissolved in the drinking water to deliver a daily dose of 30 mg/kg previously shown to lower oxidative stress [18,25], prevent endothelial dysfunction and arterial wall remodeling [6,19,24,25], and improve cognition [18]. During that period, all mice were fed a regular diet (RD, 2018; Harlan Teklad Laboratories, Madison, WI, USA).…”