AIM: To search tools of high blood pressure in the model of nitric oxide (NO)-defective hypertension, and the study focused on the effect of rilmenidine, agonist of imidazoline receptors, which was suggested to modulate central sympathetic outflow. METHODS: Three experimental groups, each consisting of 7 rats, were used: (I) rats with inhibition of NO synthase (NOS) by NG-nitro-L-arginine methyl ester (L-NAME) 40 mg·kg-1·d-1 for 4 weeks in drinking water, (II) rats with inhibited NOS as in group I , plus agonist of imidazoline receptors rilmenidine 3 mg·kg-1·d-1 for 4weeks by gavage, and(III) control rats. Systolic blood pressure wasmeasured weekly noninvasively. At the end of experiment aortic ring isometric tension was followed, NOS expression (aorta, left ventricle), and NOS activity (left ventricle and brain) were determined. RESULTS: In the group I systolic blood pressure in- creased significantly, aortic ring relaxation to acetylcholine was significantly attenuated. Rilmenidine administered simultaneously with L-NAME (group II) prevented the increase of blood pressure which did not differ significantly from control values; aortic ring relaxation to acetylcholine did not differ from control. No change in NOS expres- sion (aorta and left ventricle) was found in groups I and II. Significant decline in NOS activity (left ventricle and brain) wasfound in groups I and II. CONCLUSION: Rilmenidinehas aremarkable role inNO-defective hypertension, possibly by inhibiting central sympathetic outflow and by affecting receptors in vascular smooth muscle also. The prime cause of hypertension in this experimental model - the compromised production of NO due to inhibition of NOS - was not affected by rilmenidine. AIM: To search for high blood pressure in the model of nitric oxide (NO) -defective hypertension, and the study focused on the effect of rilmenidine, agonist of imidazoline receptors, which was suggested to modulate central sympathetic outflow. METHODS: Three experimental groups, each consisting of 7 rats, were used: (I) rats with inhibition of NO synthase (NOS) by NG-nitro-L-arginine methyl ester (L-NAME) 40 mg · kg -1 · d -1 for 4 weeks in drinking water, (II) rats with inhibited NOS as in group I, plus agonist of imidazoline receptors rilmenidine 3 mg · kg -1 · d -1 for 4 weeks by gavage, and (III) control rats. Systolic blood pressure was measured weekly At the end of experiment aortic ring isometric tension was followed, NOS expression (aorta, left ventricle), and NOS activity (left ventricle and brain) were determined. RESULTS: In the group I systolic blood pressure in- creased significantly, aortic ring relaxation to acetylcholine was significantly attenuated. R ilmenidine administered simultaneously with L-NAME (group II) prevented the increase of blood pressure which did not differ significantly from from control values; aortic ring relaxation to acetylcholine did not differ from control. No change in NOS expres- sion (aorta and left ventricle) was found in groups I and II. Significant decline in NOS activity (left ventricle and brain) was found in groups I and II. CONCLUSION: Rilmenidine is aremarkable role in NO-defective hypertension, possibly by inhibiting central sympathetic outflow and by affecting receptors in vascular smooth muscle also. The prime cause of hypertension in this experimental model - the compromised production of NO due to inhibition of NOS - was not affected by rilmenidine.