Cardiovascular effects of chronic nitric oxide synthase inhibition in genetically hypertensive rats

1. The possible role of an endothelial defect in the hypertension of the Ne w Zealand genetically hypertensive (GH) rat strain was assessed by examinin g cardiovascular responses to the nitric oxide synthase (NOS) inhibitor N-o mega-nitro-L-arginine methyl ester (L-NAME) and the endothelium-dependent d epressor agent acetylcholine (ACh). The vascular sensitivity of the hindqua rter to nitric oxide (NO) was examined using the NO donor sodium nitropruss ide (SNP). 2. N-G-Nitro-L-arginine methyl ester (10 mg/kg per day in drinking water) w as given to GH and normotensive (N) rats from age 7-9 weeks, with GH and N untreated control groups. Systolic blood pressure (tail-cuff) was monitored weekly from age 5-9 weeks. At age 9 weeks, pressure responses to various v asoactive agents were measured in vivo and in the rat isolated hindquarter. Left ventricular (LV) mass was measured at the time of death. 3. N-G-Nitro-L-arginine methyl ester induced a greater hypertensive effect in GH (P < 0.001) compared with N (P < 0.05) rats and caused a significant increase in hindquarter perfusion pressure in GH rats only (P < 0.01). 4. Genetically hypertensive rats had LV hypertrophy that was exacerbated by L-NAME (P < 0.01). Left ventricular hypertrophy was not induced by L-NAME in N rats. 5. The normalized response to ACh did not differ between GH and N control r ats and was unaffected by L-NAME treatment in vivo and in vitro except at t he highest ACh dose (3 mu g/kg) in GH hindquarters (P < 0.01). The response to SNP was similar in GH and N hindquarters and enhanced by L-NAME in GH ( 0.1 mu g; P < 0.05) and N rats (0.01 mu g, P < 0.01; 0.1 mu g, P < 0.001). 6. These results suggest that the L-arginine/NO system is not deficient in GH rats and that endothelial function in the GH hindquarter is preserved. T hey confirm that NO is involved in mediating blood pressure in GH and N rat s and raise the possibility that a non-NO-mediated mechanism may underlie A Ch-induced vasodilation in GH and N.