Premium
Nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) knockout mice display impaired renal excretory and enhanced cardiovascular responses to stress
Author(s) -
Burmeister M. A.,
Ansonoff M.,
Pintar J.,
Kapusta D. R.
Publication year - 2006
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.20.4.a359-b
Subject(s) - nop , nociceptin receptor , chemistry , medicine , endocrinology , basal (medicine) , excretion , knockout mouse , receptor , opioid peptide , opioid , insulin
Central injection of the opioid‐like peptide N/OFQ produces cardiodepressor and water diuretic responses in rats and mice that are absent in NOP knockout (−/−) mice. However, the role of the endogenous N/OFQ‐NOP system in regulating cardiovascular (CV) and renal excretory (RE) function is unknown. Here we tested the hypothesis that NOP +/+ and −/− 129S6 mice exhibit differences in CV (heart rate, HR; mean arterial pressure, MAP) and RE (urine output, V; urinary sodium excretion, UNaV) function during basal or stress states. Methods and Results In 24‐h metabolic studies NOP −/− mice had greater UNaV under basal conditions (5 day avg; −/−, n=15, 386±40; +/+, n=17, 274±31 mEq/day) and also on the second day after the diet was switched to NaCl deficient chow (−/−, n=9, 149±8; +/+, n=9, 116±16 mEq/day). In other studies, NOP −/− mice had a reduced V (−/−, n=16, 1.70±0.09; +/+, n=15, 2.14±0.12 ml/5h) and greater UNaV (−/−, 108±12; +/+, 71±14 mEq/5hr) after oral gavage (tap water). In subsequent telemetry studies no group differences in basal HR or MAP were observed. However, NOP −/− mice tended to display exaggerated CV responses to cage switching (−/−, n=3, 170±8 bpm and 29±3 mmHg; +/+, n=4, 144±14 bpm and 17±2 mmHg). Conclusions Under various basal and stressful conditions NOP −/− mice displayed an impaired ability to excrete water and/or retain Na+. Together these findings demonstrate that the endogenous N/OFQ‐NOP system participates in mediating the RE and possibly CV responses to stress. DK43337, HL 071212, DA‐09040, DA‐15237.