Rilmenidine prevents blood pressure increase in rats with compromised nitric oxide production.
OBJECTIVE
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 N(G)-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 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 increased 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 expression (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.


CONCLUSIONS
Rilmenidine has a remarkable 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.
Gerová
Mária
M
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, 813 71 Bratislava, Slovak Republic.
Török
Jozef
J
Pecháòová
Ol'ga
O
Matusková
Jana
J
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000201:enzymology; D004730:Endothelium, Vascular / Q000201:enzymology; D006352:Heart Ventricles / Q000201:enzymology; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology; D054755:Imidazoline Receptors; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000819:agonists; D000077769:Rilmenidine
D000959:Antihypertensive Agents; D054755:Imidazoline Receptors; D010080:Oxazoles; D011955:Receptors, Drug; D019001:Nitric Oxide Synthase; D000077769:Rilmenidine; D019331:NG-Nitroarginine Methyl Ester