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

Abstract Aims Rilmenidine and moxonidine are centrally acting antihypertensive agents that are more selective for I 1 -imidazoline receptors than for α 2 -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 methods 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. Key findings High-dose rilmenidine narrowed the range of the SNA response (from 89.6 ± 2.9% to 50.4 ± 7.9%, P P P P vs . –26.4 ± 5.3 mm Hg, not significant). Significance 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.