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Metabolic Stress‐Induced Renal Endothelial Dysfunction
Author(s) -
Hammoud Safaa H.,
Mougharbil Nahed,
Eid Assaad A.,
ElYazbi Ahmed F.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.512.12
Subject(s) - medicine , endocrinology , endothelial dysfunction , vasodilation , renal function , cyclooxygenase , metabolic syndrome , nitric oxide , kidney , diabetes mellitus , chemistry , biochemistry , enzyme
The burden of metabolic syndrome (MetS) is increasing globally. MetS has been shown to increase the risk for developing cardiovascular diseases, diabetes and mortality. As such, our group previously reported that perivascular adipose tissue inflammation was associated with cardiac autonomic, aortic contractile and aortic endothelial dysfunction. MetS has been also associated with high levels of kidney disease markers including glomerular filtration rate, proteinuria, and microalbuminuria. In this study, we investigated the impact of MetS on the renal endothelial function in rats fed with high caloric diet for 4, 8, and 12 weeks. Following the planned duration of high caloric intake, kidneys were isolated and perfused with physiological solution containing L‐NAME (NOS inhibitor) and diclofenac (cyclooxygenase inhibitor), and preconstricted with phenylephrine. Endothelial function was assessed as the reduction in vasodilation in response carbachol (CCh). In control rats, nitric oxide (NO) and prostaglandins were found to be the major mediators of the endothelial vasodilatory effect. On the other hand, gradual alteration in renal endothelial function was detected as the duration of the HC feeding was increased. Compared to control values, kidneys obtained from rats with HC intake showed significant increases in CCh‐induced vasodilation. Moreover, prostaglandin vasodilatory function was abolished at 8 weeks followed by loss of NO activity at 12 weeks. Additionally, the residual CCh‐induced relaxation following L‐NAME and diclofenac infusion was no longer concentration dependent, suggesting an upregulation of a poorly controlled compensatory mechanism. Studies were extended to investigate further renal changes in this rat model. HC feeding led to increased glomerular oxidative stress, mesangial expansion and glomerulosclerosis. Together, these results suggest that increasing caloric intake initiate an early progressive renal damage that could be linked to adipose inflammation. Support or Funding Information Research support: AUB‐FM grant #320148. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .