TY - JOUR
T1 - Extravascular renal denervation ameliorates juvenile hypertension and renal damage resulting from experimental hyperleptinemia in rats
AU - Oosterhuis, Nynke R
AU - Fernandes, Ramon
AU - Maicas, Nuria
AU - Bae, Sung Eun
AU - Pombo, Joaquim M.
AU - Gremmels, Hendrik
AU - Poston, Lucilla
AU - Joles, Jaap A
AU - Samuelsson, Anne Maj S
PY - 2017/12
Y1 - 2017/12
N2 - BACKGROUND: Material obesity in rodents is associated with neonatal hyperleptinemia and hypertension of sympathetic origin in adult offspring. Previously, we reported that experimentally induced hyperleptinemia in rat pups results in adulthood hypertension. Here, we addressed the hypothesis that experimental neonatal hyperleptinemia, through renal nerve activation, adversely affects adult renal function.METHOD: Sprague-Dawley male and female pups were treated with neonatal leptin (3 mg/kg, intraperitoneal) or neonatal saline, twice daily from postnatal day 9-14. Juvenile (1 month) neonatal leptin and neonatal saline rats were subjected to either bilateral renal denervation, unilateral renal denervation or Sham surgery. Arterial pressure was telemetrically monitored.RESULTS: Juvenile neonatal leptin rats with intact renal nerves demonstrated increased mean arterial pressure (MAP) accompanied by local renin-angiotensin system overactivity and reduced glomerular filtration rate. Bilateral renal denervation in rats protected against neonatal leptin-induced MAP, renal renin-angiotensin system and impaired glomerular filtration rate. A two-fold increase in sympathetically mediated tubulointerstitial damage in young adult (2 months) neonatal leptin females, was suppressed by unilateral renal denervation, independent of MAP. Neonatal leptin rats also demonstrated increases in urinary protein, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Raised blood pressure was associated with increased salt sensitivity and with sustained renal dysfunction in adulthood.CONCLUSION: We propose that neonatal hyperleptinemia programmes long-term renal structural and functional damage, through renal sympathetic nerve activation.
AB - BACKGROUND: Material obesity in rodents is associated with neonatal hyperleptinemia and hypertension of sympathetic origin in adult offspring. Previously, we reported that experimentally induced hyperleptinemia in rat pups results in adulthood hypertension. Here, we addressed the hypothesis that experimental neonatal hyperleptinemia, through renal nerve activation, adversely affects adult renal function.METHOD: Sprague-Dawley male and female pups were treated with neonatal leptin (3 mg/kg, intraperitoneal) or neonatal saline, twice daily from postnatal day 9-14. Juvenile (1 month) neonatal leptin and neonatal saline rats were subjected to either bilateral renal denervation, unilateral renal denervation or Sham surgery. Arterial pressure was telemetrically monitored.RESULTS: Juvenile neonatal leptin rats with intact renal nerves demonstrated increased mean arterial pressure (MAP) accompanied by local renin-angiotensin system overactivity and reduced glomerular filtration rate. Bilateral renal denervation in rats protected against neonatal leptin-induced MAP, renal renin-angiotensin system and impaired glomerular filtration rate. A two-fold increase in sympathetically mediated tubulointerstitial damage in young adult (2 months) neonatal leptin females, was suppressed by unilateral renal denervation, independent of MAP. Neonatal leptin rats also demonstrated increases in urinary protein, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Raised blood pressure was associated with increased salt sensitivity and with sustained renal dysfunction in adulthood.CONCLUSION: We propose that neonatal hyperleptinemia programmes long-term renal structural and functional damage, through renal sympathetic nerve activation.
KW - hypertension
KW - leptin
KW - renal injury
KW - renal nerveablation
KW - renal nerve ablation
UR - http://www.scopus.com/inward/record.url?scp=85023756706&partnerID=8YFLogxK
U2 - 10.1097/HJH.0000000000001472
DO - 10.1097/HJH.0000000000001472
M3 - Article
C2 - 28704264
SN - 0263-6352
VL - 35
SP - 2537
EP - 2547
JO - Journal of Hypertension
JF - Journal of Hypertension
IS - 12
ER -