Introduction: Rilmenidine is a widely used centrally acting antihypertensive agent. Its antihypertensive
action is due to stimulation of central I1-imidazoline receptor/α2-adrenoceptor. Since
our previous experiments showed that activation of central α2-adrenoceptors resulted
in gastroprotective effect against different types of gastric mucosal damage we aimed
to examine the effect of rilmenidine on experimental gastric ulcer.
Methods: Gastric damage was induced by ethanol. Rilmenidine was injected either intraperitoneally
(ip.) or intracerebroventricularly (icv.) 20 and 10min resp., before the ethanol challenge.
The degree of gastric damage was estimated macroscopically and characterised by ulcer
index (calculated form the number and severity of gastric mucosal lesion). Gastric
acid secretion was measured in pylorus ligated rats, the volume and acidity was measured
4h after ligation. The antagonists were injected icv. 10min before rilmenidine administration.
Results: Rilmenidine inhibited the ethenol-induced lesion given ip. (ED50: 2 nmol/kg) or icv.
(ED50: 0.006 nmol/rat). In both cases the dose-response curves proved to be bell-shaped.
Involvement of alpha-2 adrenoceptors was suggested by the antagonistic effect of yohimbine
(50 nmol/rat icv.) as well as prazosin (5 nmol/rat icv.) and ARC 239 (50 nmol/rat
icv.) (alpha-2B adrenoceptor antagonists). The involvement of endogenous opioid system
was suggested by the findings that both naloxone (5 nmol/rat icv.; µ-antagonist),
naltrindole (5 nmol/rat icv. δ-antagonist) and norbinaltorphimine (27 nmol/rat icv.;
κ-opioid receptor antagonists) highly reduced the gastro-protective effect of rilmenidine.
Furthermore, rilmenidine even in the dose of 210 nmol/rat icv. failed to affect gastric
acid secretion.
Conclusion: The centrally acting antihypertensive agent rilmenidine induces gastric mucosal protection.
The gastroprotective dose range (2–10 nmol/rat ip) is far below its antihypertensive
one (200–400 nmol/kg iv). The centrally-induced protective effect involves activation
of α2B-adrenoecptor subtypes as well as opioid system. It might be raised that antihypertensive
therapy with rilmenidine may exert beneficial action on gastric mucosa – though further
studies are needed in human beings to demonstrate the mucosal protective effect of
rilmenidine.
The work was supported by grant ETT 389/2003.
