HIGH BLOOD-PRESSURE MAINTENANCE IN TRANSGENIC MREN-2 VS LYON GENETICALLY HYPERTENSIVE RATS

The present work was aimed to assess the factors involved in the maint enance of hypertension in adult transgenic mRen-2 (TG) rats. Special a ttention was paid to the renal handling of sodium, the sympathetic, an d the renin-angiotensin system (RAS) activity. TG rats were compared w ith age-matched Lyon genetically hypertensive rats (LH), as both are o f Sprague-Dawley origin. Blood pressure (BP), heart rate, and renal sy mpathetic nerve activity (RSNA) were recorded in conscious freely movi ng animals. Kidneys were isolated and single-pass perfused at differen t pressure levels. It was observed that the peripheral sympathetic dri ve was identical in TG and LH rats as indicated by their similar 24-h urinary excretion of catecholamines and methoxylated metabolites, base line RSNA and its control by the baroreflex, and hypotensive response to ganglion-blockade. On the contrary, TG rats differed from LH rats b y a more rapid excretion of an oral isotonic sodium load, a greater hy potensive and natriuretic response to furosemide, and a more marked BP response to acute RAS blockade. The TG kidney responses to stepwise c hanges in renal perfusion pressure (RPP) differed from those of LH rat s by significantly higher perfusate flow and glomerular filtration rat e. However, the pressure natriuresis curve of TG kidneys did not diffe r from that of LH rats because of an elevated tubular sodium reabsorpt ion rate. These results suggest that adult TG rats, compared with LH r ats, exhibit a tendency toward sodium and water retention, which may e xplain that despite low renal and circulating renin levels, the RAS re mains involved in the maintenance of high BP in that model.