Even weak vasoconstriction from rilmenidine can be unmasked in vivo by opening the baroreflex feedback loop

Rilmenidine and moxonidine are centrally acting antihypertensive agents that are more selective for I₁-imidazoline receptors than for α₂-adrenergic receptors. Moxonidine previously showed a peripheral vasoconstrictive effect stronger than generally recognized, which counteracted an arterial pressure (AP) lowering effect resulting from central sympathoinhibition. We tested whether rilmenidine also showed a significant vasoconstrictive effect that could attenuate its AP lowering effect.

Efferent sympathetic nerve activity (SNA) and AP responses to changes in carotid sinus pressure were compared in nine anesthetized Wistar-Kyoto rats before and after low, medium, and high doses (40, 100, and 250 μg/kg, respectively) of intravenous rilmenidine.

High-dose rilmenidine narrowed the range of the SNA response (from 89.6 ± 2.9% to 50.4 ± 7.9%, P < 0.001) and reduced the lower asymptote of SNA (from 13.5 ± 3.0% to 2.7 ± 1.5%, P < 0.001). High-dose rilmenidine significantly increased the intercept (from 57.1 ± 3.8 to 78.2 ± 2.7 mm Hg, P < 0.001) but reduced the slope (from 0.82 ± 0.08 to 0.51 ± 0.07 mm Hg/%, P < 0.001) of the SNA-AP relationship. The reduction in the operating-point AP induced by high-dose rilmenidine did not significantly differ based on whether the peripheral effect was considered (-19.8 ± 2.2 vs. -26.4 ± 5.3 mm Hg, not significant).

Rilmenidine increased AP in the absence of SNA, which suggests a peripheral vasoconstrictive effect; however, the vasoconstrictive effect was weak and did not significantly counteract the AP-lowering effect through central sympathoinhibition.