Involvement of imidazoline receptors in the baroreflex effects of rilmenidine in conscious rabbits

Objective It has been suggested that imidazoline receptors rather than alph a (2)-adrenoceptors are involved in the sympathoinhibitory action of centra lly acting antihypertensive drugs such as rilmenidine. In the present study , we examined the relative importance of alpha (2)-adrenoceptors and imidaz oline receptors in modulating the renal sympathetic and heart rate (HR) bar oreflex in response to central administration of rilmenidine in conscious n ormotensive rabbits. Methods In seven conscious rabbits, chronically instrumented with a fourth ventricular (4V) catheter, aortic and vena caval cuff occluders and a renal nerve electrode, we continuously recorded renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and HR and assessed baroreflex MAP-RS NA and MAP-HR relationships with balloon-induced ramp rises and falls in MA P. Rabbits were treated with 4V rilmenidine (22 mug/kg) followed by 4V idaz oxan (30 mug/kg; a mixed alpha (2)-adrenoceptor and imidazoline receptor an tagonist) or 4V 2-methoxy-idazoxan (1 mug/kg; an alpha2-adrenoceptor antago nist with little affinity for imidazoline receptors). Results Rilmenidine lowered blood pressure by 24% and reduced both upper an d lower plateaus of the renal sympathetic baroreflex curve, such that the R SNA range (difference between plateaus) was reduced by 40% (-32 +/- 10 norm alized units). Curves were shifted to the left with the fall in MAP. Idazox an restored MAP, maximum RSNA and the RSNA baroreflex range. By contrast th e alpha (2)-adrenoceptor antagonist 2-methoxy-idazoxan caused only a partia l recovery of MAP and RSNA baroreflex upper plateau and range (-9 +/- 2 mmH g, 29 and 33% lower than control). Both antagonists partially restored the HR baroreflex. Conclusion These findings suggest that in conscious rabbits, both imidazoli ne receptors and alpha (2)-adrenoceptors are involved in the central antihy pertensive and baroreflex actions of rilmenidine, but that activation of im idazoline receptors is more important for its renal sympathoinhibitory acti on. (C) 2001 Lippincott Williams & Wilkins.