Effect of nitric oxide inhibition on blood pressure and renal function in TGR(mRen2)27 rats

We examined the effect of acute systemic blockade of nitric oxide synthesis on blood pressure and renal function in the monogenetically hypertensive TGR(mRen2)27 rat strain. Untreated conscious transgenic rats had significantly (p < 0.01) higher systolic blood pressures (185 ± 9 versus 130 ± 5 mm Hg) and urinary albumin excretion (32 ± 5 versus 6 ± 2 mg/day) than did control animals without evidence of renal insufficiency. Plasma and urinary nitric oxide metabolite levels did not differ between transgenic and control rats. i.v. administration of N(G)nitro-L-arginine methyl ester (10 mg/kg) to both groups caused similar elevations in systemic blood pressure (transgenic 25 ± 3 versus control 24 ± 3 mm Hg). N(G)-Nitro-L-arginine methyl ester induced reductions in whole kidney (1.4 ± 0.2 versus 0.7 ± 0.1 mL/min), and single nephron (23 ± 3 versus 11 ± 2 nL/min) glomerular filtration rates were significantly (p < 0.05) larger in transgenic than in control rats. This greater loss of GFR in transgenic animals was caused by a larger reduction in glomerular ultrafiltration coefficient (1.8 ± 0.2 versus 1.1 ± 0.1 nL·min^-1·mm Hg^-1, p < 0.05), a larger increase in afferent arteriole resistance (3.4 ± 0.2 versus 1.4 ± 0.1 dyne·s·cm^-5, p < 0.05), and a subsequently smaller rise in glomerular transcapillary pressure (10 ± 1 versus 5 ± 1 mm Hg, p < 0.05). These results indicate that the renal microvasculature and glomerular hydraulic conductivity or surface area of transgenic rats are more sensitive to nitric oxide inhibition and are consistent with an important role for nitric oxide in TGR(mRen2)27 kidney function.