Agmatine suppresses peripheral sympathetic tone by inhibiting N-type Ca(2+) channel activity via imidazoline I2 receptor activation.
Agmatine, a putative endogenous ligand of imidazoline receptors, suppresses cardiovascular function by inhibiting peripheral sympathetic tone. However, the molecular identity of imidazoline receptor subtypes and its cellular mechanism underlying the agmatine-induced sympathetic suppression remains unknown. Meanwhile, N-type Ca(2+) channels are important for the regulation of NA release in the peripheral sympathetic nervous system. Therefore, it is possible that agmatine suppresses NA release in peripheral sympathetic nerve terminals by inhibiting Ca(2+) influx through N-type Ca(2+) channels. We tested this hypothesis by investigating agmatine effect on electrical field stimulation (EFS)-evoked contraction and NA release in endothelium-denuded rat superior mesenteric arterial strips. We also investigated the effect of agmatine on the N-type Ca(2+) current in superior cervical ganglion (SCG) neurons in rats. Our study demonstrates that agmatine suppresses peripheral sympathetic outflow via the imidazoline I2 receptor in rat mesenteric arteries. In addition, the agmatine-induced suppression of peripheral vascular sympathetic tone is mediated by modulating voltage-dependent N-type Ca(2+) channels in sympathetic nerve terminals. These results suggest a potential cellular mechanism for the agmatine-induced suppression of peripheral sympathetic tone. Furthermore, they provide basic and theoretical information regarding the development of new agents to treat hypertension.
Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Young-Hwan
YH
Kim
Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Ji-Hyun
JH
Jeong
Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Duck-Sun
DS
Ahn
Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address: sschung@yuhs.ac.
Seungsoo
S
Chung
D000200:Action Potentials / Q000187:drug effects; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D004558:Electric Stimulation; D054755:Imidazoline Receptors / Q000819:agonists*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects*
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D054755:Imidazoline Receptors; D000376:Agmatine
Agmatine; Imidazoline receptor; N-type calcium channel; Sympathetic tone