Pathogenic role of angiotensin II and the NF-κB system in a model of malignant hypertensive nephrosclerosis

Hypertension Research : Official Journal of the Japanese Society of Hypertension
Victor Ferreira ÁvilaClarice Kazue Fujihara

Abstract

We previously reported that rats treated with an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), during lactation developed hypertension in adult life, without apparent functional or structural damage to kidneys, providing a new model of essential hypertension. Here, we investigated whether uninephrectomy associated with salt overload would unveil a latent renal dysfunction in this model, aggravating arterial hypertension and promoting renal injury. Male Munich-Wistar rat pups received PDTC from maternal milk (PDTCLact) from 0 to 20 days after birth. Another group received no treatment during lactation. All offspring underwent uninephrectomy (UNx) at 10 weeks of age and then were subdivided into NS, receiving a normal salt (0.5% Na+) diet, PDTCLact + NS, HS, receiving a high-salt diet (2% Na+ chow + 0.5% saline to drink), and PDTCLact+HS. Twelve weeks later, HS rats were moderately hypertensive with mild albuminuria and renal injury. In contrast, severe hypertension, glomerulosclerosis, and cortical collagen deposition were prominent in PDTCLact + HS animals, along with "onion-skin" arteriolar lesions, evidence of oxidative stress and intense renal infiltration by macrophages, and lymphocytes and angiotensin II-positive ce...Continue Reading

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Citations

Oct 28, 2019·Frontiers in Pharmacology·Vinicius Andrade-OliveiraNiels Olsen Saraiva Câmara
Mar 4, 2021·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Xiaoqian LiuYing Liang
Sep 14, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Liangli JinZhi Wang

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