Intra-Renal Angiotensin Levels Are Increased in High-Fructose Fed Rats in the Extracorporeal Renal Perfusion Model

Abstract

Overconsumption of fructose leads to metabolic syndrome as a result of hypertension, insulin resistance, and hyperlipidemia. In this study, the renal function of animals submitted to high fructose intake was analyzed from weaning to adulthood using in vivo and ex vivo methods, being compared with a normal control group. We investigated in ex vivo model of the role of the renin Angiotensin system (RAS) in the kidney. The use of perfused kidney from animals submitted to 8-week fructose treatment showed that high fructose intake caused metabolic and cardiovascular alterations that were consistent with other studies. Moreover, the isolated perfused kidneys obtained from rats under high fructose diet showed a 33% increase in renal perfusion pressure throughout the experimental period due to increased renal vascular resistance and a progressive fall in the glomerular filtration rate, which reached a maximum of 64% decrease. Analysis of RAS peptides in the high fructose group showed a threefold increase in the renal concentrations of angiotensin I (Ang I) and a twofold increase in angiotensin II (Ang II) levels, whereas no change in angiotensin 1-7 (Ang 1-7) was observed when compared with the control animals. We did not detect changes in angiotensin converting enzyme (ACE) activity in renal tissues, but there is a tendency to decrease. These observations suggest that there are alternative ways of producing Ang II in this model. Chymase the enzyme responsible for Ang II formation direct from Ang I was increased in renal tissues in the fructose group, confirming the alternative pathway for the formation of this peptide. Neprilysin (NEP) the Ang 1-7 forming showed a significant decrease in activity in the fructose vs. control group, and a tendency of reduction in ACE2 activity. Thus, these results suggest that the Ang 1-7 vasodilator peptide formation is impaired in this model contributing with the increase of blood pressure. In summary, rats fed high fructose affect renal RAS, which may contribute to several deleterious effects of fructose on the kidneys and consequently an increase in blood pressure.

Post-weaning Exposure to High-Fat Diet Induces Kidney Lipid Accumulation and Function Impairment in Adult Rats

“…To support this idea, recently our group showed in isolated perfused kidneys obtained from rats under high fructose diet, another experimental metabolic syndrome model, a progressive fall in the GFR associated by an increase in the renal concentrations of angiotensin I and angiotensin II (41). Moreover, unpublished data from our laboratory showed that angiotensin II blockade by losartan in the isolated perfused kidney method determine a higher RVR decrease more in the HD group than the ND group suggesting that the angiotensin II has an important contribution to the RVR rise in the HD.…”

Hypertension Associated with Fructose and High Salt: Renal and Sympathetic Mechanisms

“…Notably, renal angiotensin AT1 receptor mRNA was increased in adipose tissue but not kidney after three weeks of high fructose ingestion [67]. When fructose was given in greater amounts (60 to 66% in the drinking water) and for longer periods of time (8 to 16 weeks), both Ang I and Ang II as well as AT1 receptor protein expression was increased in kidney tissue [68,69]. Alternatively, the third influence on renin secretion involves sympathetic inputs to the macula densa.…”

Pathophysiological mechanisms of hypertension development induced by fructose consumption

“…Recently, Xu et al have reported that Dahl SS rats but not Dahl saltresistant rats fed with an HF diet displayed elevated BP and enhanced expression of renal PRR, renin, AGT, ACE, and AT1R. 55 Similarly, Sprague-Dawley rats with HF intake exhibited activated local RAS in the kidneys, 46,48,56,57 aorta, 56,58 skeletal muscles, 59 and adipose tissues, 18,60 as reflected by the increases of PRR, prorenin/renin, AT1R, chymase, AngI, and AngII levels in these tissues. These results imply the association between local RAS and HF-induced SSH.…”