Sympathoexcitation of moxonidine in the caudal ventrolateral medulla is dependent on I1-imidazoline receptors in anesthetized rats.
Moxonidine is a second-generation centrally acting antihypertensive drug that has a high affinity for I(1)-imidazoline receptors (I(1)R). The caudal ventrolateral medulla (CVLM), an important region involved in cardiovascular activity, contains binding sites for centrally acting drugs. Our study aimed to determine the effects of moxonidine injected into the CVLM on cardiovascular activity in anesthetized rats. Unilateral microinjection of moxonidine (0.4 and 4 nmol) into the CVLM dose-dependently increased blood pressure (BP) by 8+/-2 and 18+/-2 mmHg and renal sympathetic nerve activity (RSNA) by 19+/-3 and 48+/-5% without modifying heart rate. Microinjection of the I(1)R/alpha(2)-adrenoceptor antagonist efaroxan (4 nmol) into the CVLM produced significant decreases in baseline BP and RSNA, but also completely abolished the increases in BP (2+/-1 versus 18+/-2 mmHg, P<0.01) and RSNA (3+/-2 versus 45+/-10%, P<0.01) evoked by subsequent injection of moxonidine (4 nmol). However, prior injection of yohimbine (500 pmol), a selective antagonist of alpha(2)-adrenoceptors, into the CVLM had no significant (P>0.05) effect on the moxonidine-induced increase in BP (18+/-2 versus 17+/-3 mmHg) and RSNA (45+/-10 versus 42+/-7%). The current data suggest that moxonidine injection into the CVLM has an excitatory effect on cardiovascular activity, which is mediated by an I(1)R dependent mechanism.
Wang
Li-Gang
LG
Department of Physiology, Second Military Medical University, Shanghai 200433, China.
Gao
Lie
L
Wang
Wei
W
Yuan
Wen-Jun
WJ
Wang
Wei-Zhong
WZ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects; D013565:Sympatholytics / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D013565:Sympatholytics; C410887:imidazoline I1 receptors; D015016:Yohimbine; C043482:moxonidine; C062597:efaroxan