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

Abstract

AimsRilmenidine 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. Main methodsEfferent 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. Key findingsHigh-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). SignificanceRilmenidine 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.