Bilateral renal cryodenervation decreases arterial pressure and improves insulin sensitivity in fructose-fed Sprague-Dawley rats

Abstract

Consumption of food high in fructose is prevalent in modern diets. One week of moderately high fructose intake combined with high salt diet has been shown to increase blood pressure and failed to suppress plasma renin activity (PRA). We tested the hypothesis that the hypertension and high PRA are consequences of elevated renal sympathetic nerve activity (RSNA). In protocol 1, we assessed RSNA by telemetry in conscious Sprague-Dawley rats given 20% fructose or 20% glucose in drinking water on a 0.4% NaCl diet (NS) for 1 wk and then transitioned to a 4% NaCl diet (HS). After an additional week, mean arterial pressure (MAP) and RSNA increased significantly in fructose-fed but not glucose-fed HS rats. In protocol 2, fructose (Fruc)- or glucose (Glu)-fed rats on NS or HS diet for 3 wk underwent sham denervation (shamDNX) or bilateral renal denervation using cryoablation (cryoDNX). MAP was higher in Fruc-HS rats compared with Glu-NS, Glu-HS, or Fruc-NS rats and decreased after cryoDNX ( P < 0.01). MAP did not change in Fruc-HS shamDNX rats. Renal norepinephrine content decreased by 85% in cryoDNX ( P < 0.01 vs. shamDNX). PRA significantly decreased after cryoDNX in both Fruc-NS and Fruc-HS rats. Nonfasting blood glucose levels were similar among the four groups. Glucose-to-insulin ratio significantly increased in Fruc-HS cryoDNX rats, consistent with greater insulin sensitivity. Taken together, these studies show that renal sympathoexcitation is, at least in part, responsible for salt-dependent increases in MAP, increased PRA, and decreased insulin sensitivity in rats fed a moderately high fructose diet for as little as 3 wk.

<p>Aortic Stiffness and Diastolic Dysfunction in Sprague Dawley Rats Consuming Short-Term Fructose Plus High Salt Diet</p>

“…The present studies confirm previous findings from our own 9 and other laboratories 6 , 8 , 10 showing that consumption of fructose at levels comparable to that ingested by the upper 20th percentile of the human population combined with high salt intake results in elevated arterial pressure. Although the increase in arterial pressure is modest when assessed in conscious unstressed rats by telemetry (vs tail cuff where in there is the additional stress component of mild restraint), it is nonetheless reproducible, significant, and sustained.…”

“…Sympathetic innervation of the aorta is now recognized as a factor in aortic stiffening, 54 and fructose-fed high salt rats display heightened renal sympathetic nerve activity. Renal denervation prevents the hypertension in this and other rodent models 9,55 and ameliorates PWV in animal 55 and human systolic hypertension. 56 The contribution of cellular metabolic changes or ioninduced contractility cannot be totally excluded since triglycerides and cumulative salt balance are elevated in this model.…”

“…Three to five days later, hemodynamic telemetry devices were implanted and rats allowed to recover for three-four days in single housing. Following previously established protocols, 6,9,10 the rats were randomized to either 20% (w/ v) glucose (Sigma-Aldrich, St. Louis, MO) or 20% (w/v) fructose (Sigma-Aldrich, St. Louis, MO) and maintained 0.4% NaCl chow. The age of rats at enrollment was 10-12 weeks and the average weight was 228.6 ± 5.9 g in the control group and 225 ± 2.5g in the Tempol group.…”

“…In the present investigation, we employed the fructoseinduced salt-sensitive hypertension rat model by feeding rats 20% (w/v) fructose for one week, followed by the addition of 4% NaCl for three more weeks, which results in increases in mean arterial pressure. 9 We hypothesized that dietary fructose, rather than glucose, in combination with high salt will lead to aortic stiffening, evidenced by increased aortic PWV, decreased strain, and decreased distensibility coefficient. This will, in turn, result in an increase in RRI.…”

“… 6 , 7 Activation of the renin-angiotensin-aldosterone system (RAAS) and increased renal sympathetic nerve activity, both of which promote increased renal tubular sodium reabsorption, have also been implicated as mechanisms resulting in elevated arterial pressure. 6 , 8 - 11 Notably, bilateral renal cryo-denervation 9 or daily treatment with the superoxide dismutase mimetic, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (+T; Tempol), reduces 8-isoprostane excretion and ameliorates the hypertension. 10 In light of these findings, it is possible that combined fructose and high salt diet may exert a deleterious impact on cardiac and vascular function either directly or indirectly via the elevated arterial pressure.…”