Premium
Mass spectrometric quantification of prostaglandin D2 levels in choroid plexus, cerebrospinal fluid and rostral ventrolateral medulla link PGD2 signaling to the development of neurogenic hypertension (1140.10)
Author(s) -
AsirvathamJeyaraj Ninitha,
Jones A Daniel,
Fink Gregory
Publication year - 2014
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.28.1_supplement.1140.10
Subject(s) - chemistry , choroid plexus , medicine , endocrinology , prostaglandin , cerebrospinal fluid , subfornical organ , prostaglandin d2 , solitary tract , arachidonic acid , prostaglandin e , angiotensin ii , central nervous system , enzyme , blood pressure , biochemistry
Roles of Prostaglandin (PG) D2 signaling in blood pressure (BP) control are obscure. PGD2 is synthesized from precursor arachidonic acid and PGH2 by the action of enzyme lipocalin‐prostaglandin D synthase (L‐PGDS). Choroid plexus lining the third ventricle (3VCP) and cerebrospinal fluid (CSF) from AngII‐salt hypertensive (AngII‐HS‐HTN) rats express high mRNA and protein levels of L‐PGDS. Blocking the L‐PGDS enzyme centrally with its antagonist AT56 attenuates AngII‐salt‐HTN development. So we hypothesized that increased PGD2 synthesis in the brain is central to AngII‐salt mediated increase in BP. Method: Two sets of experiments were performed. In one set of high salt (HS, 2%) fed rats, vehicle or AngII (150 ng/kg/min, sc) was infused. In another set of HS fed rats, L‐PGDS was first blocked chronically with different doses (nmol‐h ‐1 , sc) of AT56 (0.6,6,23) and then AngII was infused. From both studies, brain tissue and CSF were collected on day 4 of AngII infusion for ultra performance liquid chromatography‐tandem mass spectrometric analysis of substrate arachidonic acid (AA) and metabolites PGD2, PGJ2, delta12‐PGJ2 and PGE2. Result: HS and AngII compared to vehicle controls (p<0.05) increased the levels of substrate AA in 3VCP. HS and AngII significantly increased the metabolite PGD2 in 3VCP, CSF and rostral ventrolateral medulla (RVLM) compared to vehicle controls. This increase in PGD2 was inhibited in the RVLM of rats treated with AT56 at doses (6 and 23 nmol‐h ‐1 , sc) that were previously observed to attenuate AngII‐HS‐HTN. There was with no change in the levels of metabolites PGJ2, delta12‐PGJ2 and PGE2 with HS and AngII treatment. Conclusion: Increased PGD2 synthesis and signaling in the 3VCP, CSF and RVLM mediate development of AngII‐salt HTN.AA‐3VCP(ng/region ± SE) PGD2‐3VCP(ng/region ± SE) PGD2‐RVLM(ng/region ± SE) PGD2‐CSF (pg/ml ± SE) HS Vehicle 333 ± 80 0.8 ± 0.4 0.3 ± 0.1 193 ± 39 HS AngII 3057 ± 1163 10.3 ± 4 9 ± 1 418 ± 51Grant Funding Source : RO1 HL 076312 and RCO HL 060363