title: Chronic recurrent dehydration associated with periodic water intake exacerbates hypertension and promotes renal damage in male spontaneously hypertensive rats.
abstract: Epidemiological evidence links recurrent dehydration associated with periodic water intake with chronic kidney disease (CKD). However, minimal attention has been paid to the long-term impact of periodic water intake on the progression of CKD and underlying mechanisms involved. Therefore we investigated the chronic effects of recurrent dehydration associated with periodic water restriction on arterial pressure and kidney function and morphology in male spontaneously hypertensive rats (SHR). Arterial pressure increased and glomerular filtration rate decreased in water-restricted SHR. This was observed in association with cyclic changes in urine osmolarity, indicative of recurrent dehydration. Additionally, water-restricted SHR demonstrated greater renal fibrosis and an imbalance in favour of pro-inflammatory cytokine-producing renal T cells compared to their control counterparts. Furthermore, urinary NGAL levels were greater in water-restricted than control SHR. Taken together, our results provide significant evidence that recurrent dehydration associated with chronic periodic drinking hastens the progression of CKD and hypertension, and suggest a potential role for repetitive bouts of acute renal injury driving renal inflammatory processes in this setting. Further studies are required to elucidate the specific pathways that drive the progression of recurrent dehydration-induced kidney disease.
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria, 3800, Australia.
authors.forename: Lucinda M
authors.initials: LM
authors.lastname: Hilliard
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria, 3800, Australia.
authors.forename: Katrina M Mirabito
authors.initials: KM
authors.lastname: Colafella
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria, 3800, Australia.
authors.forename: Louise L
authors.initials: LL
authors.lastname: Bulmer
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, 3800, Australia.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Puelles
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria, 3800, Australia.
authors.forename: Reetu R
authors.initials: RR
authors.lastname: Singh
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria, 3800, Australia.
authors.forename: Connie P C
authors.initials: CP
authors.lastname: Ow
authors.affiliation: Department of Pharmacology, Monash University, Melbourne, Victoria, 3800 Australia.
authors.forename: Tracey
authors.initials: T
authors.lastname: Gaspari
authors.affiliation: Department of Pharmacology, Monash University, Melbourne, Victoria, 3800 Australia.
authors.forename: Grant R
authors.initials: GR
authors.lastname: Drummond
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria, 3800, Australia.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Evans
authors.affiliation: Department of Pharmacology, Monash University, Melbourne, Victoria, 3800 Australia.
authors.forename: Antony
authors.initials: A
authors.lastname: Vinh
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria, 3800, Australia.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Denton