Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas

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• 作者：Edna Aparecida Silveira ; Fabiana Dayse Magalh茫es Siman ; Tha铆s de Oliveira Faria ; Marcos Vin铆cius Alto茅 Vescovi ; Lorena Barros Furieri ; Juliana Hott F煤cio Lizardo ; Ivanita Stefanon ; Aless ; ra Sim茫o Padilha ; Dalton Valentim Vassallo
• 关键词：Lead acetate ; Hypertension ; Rat aorta ; NO ; ROS ; Vasoconstrictor prostanoids ; Local renin&ndash ; angiotensin system ; Free radicals
• 刊名：Free Radical Biology and Medicine
• 出版年：February, 2014
• 年：2014
• 卷：67
• 期：Complete
• 页码：366-376
• 全文大小：1649 K

文摘

Chronic lead exposure induces hypertension affecting endothelial function. We investigated whether low-concentration lead exposure alters blood pressure and vascular reactivity, focusing on the roles of NO, oxidative stress, cyclooxygenase-derived vasoconstrictor prostanoids, and the local angiotensin-renin system. Aortic rings from 3-month-old Wistar rats were treated daily with lead acetate (first dose 4 mg/100 g, subsequent doses 0.05 mg/100 g, im) or vehicle for 30 days. Treatment increased lead blood levels (12 渭g/dl), blood pressure, and aortic ring contractile response to phenylephrine (1 nM-100 mM). Contractile response after L-NAME administration increased in both groups but was higher after lead treatment. Lead effects on R_max decreased more after apocynin and superoxide dismutase administration compared to control. Indomethacin reduced phenylephrine response more after lead treatment than in controls. The selective COX-2 inhibitor NS398, thromboxane A₂/prostaglandin H2 receptor antagonist SQ 29,548, TXA₂ synthase inhibitor furegrelate, EP₁ receptor antagonist SC 19220, and ACE inhibitor and AT₁ receptor antagonist losartan reduced phenylephrine responses only in vessels from lead-treated rats. Basal and stimulated NO release was reduced and local O₂^{鈭?/sup> liberation increased in the lead-treated group compared to controls. eNOS, iNOS, and AT₁ receptor protein expression increased with lead exposure, but COX-2 protein expression decreased. This is the first demonstration that blood Pb2+ (12 碌g/dl) concentrations below the WHO-established values increased systolic blood pressure and vascular phenylephrine reactivity. This effect was associated with reduced NO bioavailability, increased reactive oxygen species production, increased participation of COX-derived contractile prostanoids, and increased renin-angiotensin system activity.}