Premium
Hypertensive Dahl salt‐sensitive rats produce a blunted diuresis to central N/OFQ which is restored by CNS G‐alpha q protein knockdown
Author(s) -
Wainford Richard David,
Kapusta Daniel R
Publication year - 2008
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.22.1_supplement.1161.4
Subject(s) - diuresis , endocrinology , medicine , chemistry , vasopressin , nociceptin receptor , renal function , receptor , opioid , opioid peptide
Hypertensive Dahl salt‐sensitive (DSS) rats on high NaCl intake have enhanced plasma vasopressin (AVP). We examined whether DSS rats can effectively excrete water following intracerebroventricular (i.c.v.) injection of nociceptin/orphanin FQ (N/OFQ), a peptide that evokes profound diuresis via inhibition of AVP release. Methods Changes in CV and renal excretory function produced by i.c.v. N/OFQ (5.5 nmol) were examined in conscious chronically instrumented DSS rats maintained (3 weeks) on 8% NaCl (N=6) or normal chow (N=6). Separate animals fed 8% NaCl diet (N=6), were pretreated with a Gαq oligodeoxynucleotide (ODN) (25 μg), which we have shown participates in the recovery (AVP stimulatory) phase following the peak diuresis to N/OFQ. MAP and HR were recorded and urine collected during control and for 80‐min (10‐min periods) following i.c.v. N/OFQ. Results Dahl SS rats fed an 8% NaCl diet became hypertensive (normal chow, MAP 128 ± 4 mmHg; 8% NaCl chow, 169 ± 7 mmHg, P< 0.05). The diuresis to i.c.v. N/OFQ was blunted in duration and magnitude in hypertensive DSS rats (peak diuresis; normotensive DSS 50‐min, 174 ± 18 μl/min; hypertensive DSS 30‐min, 110 ± 17 μl/min, P< 0.05). In hypertensive DSS rats, i.c.v. Gαq pre‐treatment fully restored the diuresis to i.c.v. N/OFQ (peak; DSS + Gαq ODN 50‐min, 170 ± 14 μl/min P< 0.05). Conclusion Hypertensive DSS rats produced a blunted diuresis to i.c.v. N/OFQ, which was restored to a normal diuretic pattern by prior central Gαq protein knockdown. Thus, in DSS rats, high NaCl may enhance central Gαq protein expression and attenuate the inhibitory effects of this, and possibly other Gαq‐protein coupled receptor ligands on AVP secretion. DK43337, HL 071212, P20 RR018766