Abstract 120: Central Prostaglandin D Synthase Inhibition Blocks Development of Chronic Angiotensin II-salt Hypertension in the Rat.
Hypertension (HT) is still the major risk factor for various cardiovascular diseases. Previously we found that central cyclooxygenase-1 (COX-1) inhibition prevented the development of angiotensin II (AngII)-salt HT and sympathetic hyperactivity in Sprague Dawley rats. We found a significant up-regulation of prostaglandin D synthase (PGDS) mRNA levels in the organum vasculosum lamina terminalis, a circumventricular organ. This was accompanied by a significant increase in the protein levels of PGDS in the choroid plexus lining the ventricles. Therefore we hypothesized that the enzyme, PGDS is critical for the development of HT in this model. To test this hypothesis, adult male Sprague Dawley rats were implanted with radio-telemeters for hemodynamic measurements. After 3 days of basal recordings, rats on 2% NaCl diet were pretreated with vehicle or AT56, a PGDS inhibitor (10mg/kg, ICV) through a mini-osmotic pump. From day 8, all rats received AngII (150 ng/kg/min, s.c.). In vehicle-treated rats, mean arterial pressure (MAP) rose significantly. Rats that received AT56 showed attenuation of MAP compared to vehicle-treated rats (p<0.05). To examine if PGDS drives sympathetic nerve activity in this model, we treated these animals with the ganglionic blocker, hexamethonium (30mg/kg BW, i.p.) on day 14. In AT56-treated rats, fall in MAP was significantly lower than that of the control rats after ganglionic blockade. We conclude that PGDS products or the enzyme by itself is critical for the development of AngII-salt sympathoexcitation and HT.
- © 2012 by American Heart Association, Inc.