Sympathoinhibitory Action of Rilmenidine in Conscious Sinoaortically Denervated Rats

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Abstract
The responses of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to rilmenidine administration and changes in these responses after idazoxan or yohimbine pretreatment were investigated in conscious sinoaortically denervated rats. Intravenous (i.v.) injection of rilmenidine (300 and 600 micrograms/kg) dose-dependently reduced MAP (16 and 24%, respectively) and RSNA (31 and 56%, respectively), whereas bradycardia was similar at both doses of the drug. Intracisternal (i.c.) pretreatment with idazoxan (5 micrograms/kg), alpha 2-adrenoceptor antagonist with a high affinity to imidazoline receptors (IR) prevented rilmenidine-induced decreases in MAP but not in RSNA and HR. Rilmenidine (300 micrograms/kg i.c.) significantly decreased MAP by 24%, RSNA by 32%, and HR by 13%. Pretreatment with idazoxan (1 microgram/kg i.c.) significantly attenuated the hypotensive and sympathoinhibitory effects of rilmenidine, whereas i.c. pretreatment with equimolar to 10-fold higher doses of yohimbine, an alpha 2-antagonist that binds poorly with IR, did not. Both idazoxan and yohimbine failed to affect the rilmenidine-induced bradycardia, however. We concluded that (a) rilmenidine exhibits more marked hypotensive effect when injected i.c. than when injected i.v., (b) a part of the inhibitory effect of i.v.-injected rilmenidine on RSNA may be exerted through idazoxan-insensitive mechanisms which might be activated by peripheral action of the drug, and (c) the hypotensive action of rilmenidine relates more to the interaction with IR than with alpha 2-adrenoceptors.

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