Abstract 119: Central Phospholipase A2, Cyclooxygenase-1, Prostaglandin D Synthase and DP1 Receptor Expression During the Development of Angiotensin II-salt Hypertension

Abstract

Chronic angiotensin II (Ang II) infusion combined with high salt in the diet has been used to study the development of Hypertension (HT). We have found that cyclooxygenase (COX) inhibition during the early stages of Ang II infusion prevented the development of HT and sympathetic hyper-activity in AngII-salt model. It is likely that these changes are mediated through alterations in the levels of COX and related enzymes. Therefore, we hypothesized that enzymes such as phospholipase A2 (PLA2), prostaglandin D synthase (PGDS) and COX-1 may be altered in specific brain regions to promote AngII-salt HT. To test this, adult male Sprague Dawley rats were implanted with radio-telemeters and placed on a 2% NaCl diet. They were infused with Ang II (150 ng/kg/min, sc) or the vehicle after obtaining 3 days of basal recording. Mean arterial pressure was significantly elevated in AngII-treated animals compared to controls. Animals were sacrificed 4 days after Ang-II infusion. The brains were removed, frozen and sectioned. Middle cerebral artery (MCA), paraventricular nucleus (PVN), organum vasculosum lamina terminalis (OVLT), subfornical organ (SFO), rostral ventrolateral medulla (RVLM) and choroid plexus (CP) were dissected and processed for western blotting. Western blot analysis showed a significant up-regulation of PLA2 in the MCA, PGDS in the choroid plexus. However, there was no change in the protein levels of COX in AngII treated rats. Next, we measured the levels of PGDS receptor, DP1 and found up-regulation of the receptor in the PVN. The results indicated that there is alteration in the protein levels of PLA2, PGDS and DP1 during the early stages of HT development in this model. This altered protein expression could be critical in driving the development of AngII-salt HT.