Premium
Thick Ascending Limb‐Specific NOS1 Knockout Reduces Urinary Osmolality in Type 1 Diabetes
Author(s) -
Edenfield Leia A,
De Miguel Carmen,
Musall Benjamin C,
Harrison David G,
Carmines Pamela K,
Pollock Jennifer S
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.910.12
Subject(s) - endocrinology , medicine , nos1 , urine osmolality , chemistry , osmole , excretion , nitric oxide synthase , nitric oxide
Diabetic (T1D) animal models show upregulated nitric oxide (NO) production and NO synthase 1 (NOS1) activity in renal medullary thick ascending limb (TAL). Because NO reduces Na + transport by the TAL, we hypothesized that TAL‐specific NOS1 knockout (KO) mice develop fluid‐electrolyte dysfunction with T1D. NOS1 flox (n=10–12) and TAL NOS1 KO mice (n=6–9) were administered streptozotocin (STZ; 150 mg/kg, ip), and systolic blood pressure (SBP), electrolytes, and urine osmolality monitored. After 7 wks of T1D, NOS1 flox and TAL NOS1 KO mice did not differ with regard to SBP (119±4 vs 120±3 mmHg), blood glucose (460±58 vs 511±42 mg/dl), body weight (25.0±1.6 vs 24.5±0.9 g), water consumption (8.3±3.5 vs 14.6±4.2 ml/day) or protein excretion (3.5±1.4 vs 4.12±0.8 mg protein/day). Post‐T1D urine flow was greater in TAL NOS1 KO than NOS1 flox mice (9.5±3.3 vs 5.0±2.3 ml/day; p=0.04). T1D led to reduced urinary osmolality in TAL NOS1 KO mice (Baseline=2832±448 mOsm/kg; T1D=1287±195 mOsm/kg; p<0.05), an effect significantly different from NOS1 flox mice (Baseline=2625±270 mOsm/kg; T1D=2117± 228 mOsm/kg; p (genotype x T1D) <0.05). T1D did not alter Na + or K + excretion in either group. In conclusion, the loss of NOS1 in the TAL altered TID‐induced urine output and osmolality suggesting that TAL NOS1‐derived NO is critical to maintain fluid‐electrolyte homeostasis during T1D.