NITRIC-OXIDE SYNTHASE INHIBITION WITH N-OMEGA-NITRO-L-ARGININE METHYL-ESTER AFFECTS BLOOD-PRESSURE AND CARDIOVASCULAR STRUCTURE IN THE GENETICALLY HYPERTENSIVE RAT STRAIN

1. Inhibition of nitric oxide (NO) synthesis with the nitric oxide syn thase (NOS) inhibitor NW-nitro-L -arginine methyl ester (L-NAME) was u sed as a tool to investigate further a possible endothelial defect in the New Zealand genetically hypertensive (GR) rat strain compared with its normotensive (N) control strain. 2. N-omega-nitro-L-arginine meth yl ester was given to GH and N groups in their drinking water from age 7-10 weeks (10 mg/kg per day for weeks 1 and 2 and then 5 mg/kg per d ay for week 3), Tail-cuff blood pressure (BP) was measured meekly and at the end of the experiment the mesentery was fixed by perfusion, sec ond order branches of the mesenteric artery were embedded in Technovit and stained sections were used to quantify the structure of the mesen teric resistance arteries (MRA). The heart was removed and weighed for determination of left ventricular (LV) mass. 3. In GH rats, BP and LV mass were significantly raised by L-NAME, while in N rats L-NAME trea tment significantly elevated BP, but had no effect on LV mass.4. In GH rats, the media width was significantly increased by L-NAME treatment (P<0.01); lumen diameter remained unchanged, Thus, the ratio of media width/lumen diameter (M/L) was significantly increased by exacerbatio n of the hypertrophic outward remodelling characteristic of the GK str ain, There were no significant changes in the Mn ratio in L-NAME-treat ed N rats. 5. Thus, in the GH strain, cardiovascular structure is more sensitive to NOS inhibition than either its N control strain or (on e vidence from the literature) the spontaneously hypertensive rat strain .