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Vasopressin Mediates the Renal Damage Induced by Limited Fructose Rehydration in Recurrently Dehydrated Rats.

ABSTRACT: Recurrent dehydration and heat stress cause chronic kidney damage in experimental animals. The injury is exacerbated by rehydration with fructose-containing beverages. Fructose may amplify dehydration-induced injury by directly stimulating vasopressin release and also by acting as a substrate for the aldose reductase-fructokinase pathway, as both of these systems are active during dehydration. The role of vasopressin in heat stress associated injury has not to date been explored. Here we show that the amplification of renal damage mediated by fructose in thermal dehydration is mediated by vasopressin. Fructose rehydration markedly enhanced vasopressin (copeptin) levels and activation of the aldose reductase-fructokinase pathway in the kidney. Moreover, the amplification of the renal functional changes (decreased creatinine clearance and tubular injury with systemic inflammation, renal oxidative stress, and mitochondrial dysfunction) were prevented by the blockade of V1a and V2 vasopressin receptors with conivaptan. On the other hand, there are also other operative mechanisms when water is used as rehydration fluid that produce milder renal damage that is not fully corrected by vasopressin blockade. Therefore, we clearly showed evidence of the cross-talk between fructose, even at small doses, and vasopressin that interact to amplify the renal damage induced by dehydration. These data may be relevant for heat stress nephropathy as well as for other renal pathologies due to the current generalized consumption of fructose and deficient hydration habits.

SUBMITTER: Garcia-Arroyo FE

PROVIDER: S-EPMC5599902 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Vasopressin Mediates the Renal Damage Induced by Limited Fructose Rehydration in Recurrently Dehydrated Rats.

García-Arroyo Fernando E FE Tapia Edilia E Blas-Marron Mónica G MG Gonzaga Guillermo G Silverio Octaviano O Cristóbal Magdalena M Osorio Horacio H Arellano-Buendía Abraham S AS Zazueta Cecilia C Aparicio-Trejo Omar Emiliano OE Reyes-García Juan G JG Pedraza-Chaverri José J Soto Virgilia V Roncal-Jiménez Carlos C Johnson Richard J RJ Sánchez-Lozada Laura G LG

International journal of biological sciences 20170718 8

Recurrent dehydration and heat stress cause chronic kidney damage in experimental animals. The injury is exacerbated by rehydration with fructose-containing beverages. Fructose may amplify dehydration-induced injury by directly stimulating vasopressin release and also by acting as a substrate for the aldose reductase-fructokinase pathway, as both of these systems are active during dehydration. The role of vasopressin in heat stress associated injury has not to date been explored. Here we show th ...[more]

PMID: 28924378

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Project description:ObjectiveOur laboratory previously published that long-term administration of estradiol (E2) was detrimental to the kidneys of midlife ovariectomized Long Evans rats, contrasting clinical studies in showing that menopausal hormone therapy is associated with decreased albuminuria. However, it is unknown whether this renal benefit was due to estrogen and/or the combination with progestogen. Therefore, the objective of the current study was to determine the impact of medroxyprogesterone (MPA) on E2-mediated renal damage using a rodent model.MethodsFemale Long Evans retired breeders underwent ovariectomy at 11 months of age and were treated for 40 days with subcutaneous E2, E2+MPA or vehicle at doses mimicking that of menopausal hormone therapy (N = 5-7 per group). Systolic blood pressure was measured along with indices of renal damage and function to investigate the impact of MPA on E2-mediated renal outcomes. Renal estrogen receptor alpha and G protein-coupled estrogen receptor transcript copy numbers were measured in all treatment groups through droplet digital PCR.ResultsMiddle-aged female Long Evans rats displayed spontaneous hypertension with similar systolic blood pressures and heart weights between groups. Even though blood pressure was comparable, E2 reduced glomerular filtration rate and increased proteinuria indicating pressure-independent renal damage. Coadministration with MPA prevented E2-induced glomerular filtration rate impairment and proteinuria by promoting renal hypertrophy and preventing renal interstitial fibrosis. Both E2 and E2+MPA reduced renal estrogen receptor alpha (ERα) and increased renal G protein-coupled estrogen receptor mRNA, but neither ERα nor ERß protein was different between groups.ConclusionMPA was protective against E2-induced renal damage and dysfunction in middle-aged female Long Evans rats. Assessing the impact of hormone therapy on renal outcomes may be an important clinical factor when considering treatment options for postmenopausal women.

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Dataset Information

Vasopressin Mediates the Renal Damage Induced by Limited Fructose Rehydration in Recurrently Dehydrated Rats.

Publications

Vasopressin Mediates the Renal Damage Induced by Limited Fructose Rehydration in Recurrently Dehydrated Rats.

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