DEPRESSOR ROLE OF ANGIOTENSIN AT(2) RECEPTORS IN THE (MREN-2)27 TRANSGENIC RAT

The (mRen-2)27 transgenic rat (Tg(+)), a hypertensive model dependent on increased expression of the renin angiotensin system, was used to e xplore the role of angiotensin AT(2) receptors in the control of cardi ovascular and renal excretory function. Experiments tested the effect of blockade of AT(2) receptors on basal blood pressure and the presser , renal excretory, and vasopressin (VP) responses to intravenous hyper tonic saline (HS). Chronically catheterized male Tg(+) and normotensiv e Sprague-Dawley rats (Tg(-)) were housed in metabolic cages. PD123319 (AT(2) antagonist) or 0.9% NaCl was given by intravenous bolus (3 mg/ kg) followed by infusion (50 mu g/kg/min). Blockade of AT(2) receptors both in Tg(+) and Tg(-) rats produced no change in basal mean arteria l pressure (MAP). The presser response to intravenous HS (10% NaCl; 32 3 mu L/100 g body weight) was significantly greater in Tg(+) than in T g(-) rats. PD123319 did not affect the peak rise in MAP but extended t he time course of the response only in Tg(+) rats. MAP was increased 3 9 +/- 4 and 36 +/- 3 mm Hg in Tg(+) rats with and without the antagoni st as compared to 20 +/- 2 and 24 + 2 mm Hg in Tg(-) rats. In the anta gonist-treated Tg(+) rats, MAP remained elevated for 60 min as compare d to 5 min for Tg(+) control or Tg(-) control or antagonist-treated ra ts. Hypertonic saline caused similar increases in plasma Na, VP, and i n the natriuretic and diuretic responses in both Tg(+) and Tg(-) rats, with no effect of antagonist treatment. These results demonstrate tha t Tg(+) rats are sensitive to the effects of peripheral osmotic stimul ation showing an increased presser response, not attributed to greater secretion of VP or diminished natriuresis. These data also suggest th at angiotensin AT(2) receptors play a depressor role in the sodium-ind uced presser response in this model. (C) 1998 American Journal of Hype rtension, Ltd.