Abstract
In this study, it was aimed to investigate the role of serotonergic neurotransmission in nucleus tractus solitarius (NTS) for the central regulation of blood pressure and heart rate and its involvement in baroreceptor reflex activation in rats. A microinjection of 5-hydroxytryptamine (5-HT) into the NTS produced decreases in blood pressure and heart rate. Maximal decreases were $34.4{\pm}1.6$ mmHg and $41.7{\pm}10.2$ beats per min by 300 pmol of 5-HT. Microinjections of ${\alpha}-methylnor-adrenaline$ $({\alpha}-MNE)$ and clonidine manifested similar decreases in blood pressure and heart rate. The hypotensive and bradycardial effects of 5-HT were blocked by previous applications of 5-HT antagonists, ritanserin, methysergide and ketanserin into the NTS, respectively. By pretreatment with reserpine and 6-hydroxydopamine (6-OHDA, i.c.v.), both hypotensive and bradycardial effects of 5-HT were significantly attenuated. Pretreatment with 5, 7-dihydroxytryptamine (5,7-DHT, i.c.v.) enhanced the hypotensive and bradycardial effects of 5-HT. Similarly, following pretreatment with 6-OHDA, the effects of clonidine were increased. Pretreatment either with 5,7-DHT or 6-OHDA significantly attenuated the sensitivity of baroreflex produced either by phenylephrine or by sodium nitroprusside. When either 5,7-DHT or 6-OHDA was injected into the NTS $(5,7-DHT;\;8{\mu}g\;6-OHDA;\;10{\mu}g)$, both of the baroreflex sensitivities were impaired. In the immunohistochemical study, the injection of 6-OHDA into the the NTS led to reduction of axon terminal varicosity, however, the injection did not reduce the numbers of catecholaminergic cell bodies. Likewise, when 5,7-DHT was injected into the NTS, the varicosity of serotonergic axon terminals was markedly reduced. Based on these results, it is suggested that (1) stimulation of serotonergic receptors in the NTS leads to decreases in blood pressure and heart rate as observed with the stimulation of catecholaminergic system, (2) both serotonergic and catecholaminergic receptors may be located postsynaptically, and (3) the serotonergic neurons as well as catecholaminergic neurons may have a close relevance for the activation of baroreflex.
혈압 및 심박동수 조절에 대한 serotonin성 기전의 역할을 흰쥐 뇌의 NTS에서 검토하고 catecholamine성 기전과 비교하여 다음과 같은 결과를 얻었다. 1) 5-HT를 NTS에 주사시 혈압 및 심박동수는 감소되었고, 5-HT 300 pmol을 NTS에 주사하였을 때 가장 현저하게 하강하였다. ${\alpha}-MNE$과 clonidine도 마찬가지로 혈압과 심박동수의 감소를 일으켰다. 5-HT의 효과는 5-HT 수용체 길항제인 ritanserin, methysergide 및 ketanserin의 전처치에 의하여 봉쇄되었다. 2) Reserpine과 6-OHDA를 전처치하였을 때는 5-HT에 의한 혈압 및 심박동수 감소가 현저하게 약화되었다. 3) 5,7-DHT 전처치 후에는 5-HT에 의한 혈압 및 심박동수 감소는 증가하였다. 한편 6-OHDA 전처치에 의하여서도 clonidine의 혈압 및 심박동수 감소 현상은 항진하였다. 4) 5,7-DHT와 6-OHDA를 i.c.v.로 전처치하였을 때 phenylephrine과 sodium nitropursside에 의한 압반사 감수성은 현저히 저하하였고, 이들을 NTS로 주사시도 압반사 감수성이 손상되었다. 5) Immunohistochemistry에 의해 NTS에서 catecholamine성 세포체, 신경축색 말단과 serotonin성 신경축색 말단을 관찰하였고, 6-OHDA 주사후에 catecholamine성 신경축색 말단의 varicosity는 현저히 감소하였다. 한편 5,7-DHT처치에 의하여서는 serotonin성 신경축색 말단의 varicosity가 현저히 감소하였다. 이상의 실험 결과, NTS에 있는 serotonin성 수용체의 활성에 의하여 (1) 혈압 및 심박동수 감소가 일어나며, (2) 이는 catecholamine성 신경계와 관련되어 야기되며, (3) serotonin과 catecholamine성 수용체는 NTS의 postsynaptic site에 존재하고, (4) serotonin과 catecholamine성 신경세포는 압반사 조절에 있어서 중요한 역할을 하는 것으로 사료된다.
(Department of Pharmacology, College of Medicine, Pusan National University)
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