Yasunori Hatayama

Role of Central Serotonergic (5-HT2) Receptor in Blood Pressure Regulation in Rats

To investigate the role of the serotonergic nervous system in blood pressure regulation, 5 micrograms of 5-hydroxytryptamine (5-HT) was given i.c.v. before and after 1 microgram of i.c.v. xylamidine or 200 micrograms of i.c.v. ketanserin or 200 micrograms of i.v. ketanserin in conscious Wistar Kyoto rats. Also i.v. (0.5, 1, 2 micrograms) or i.c.v. (1 microgram) phenylephrine (PHE) were given before and after 1 microgram of i.c.v. xylamidine. I.c.v. 5-HT elicited a consistent pressor response of approximately 27mmHg and slight decrease in heart rate. MAP and heart rate did not change after xylamidine or ketanserin. Whereas pressor response to i.c.v. 5-HT after i.c.v. ketanserin or i.c.v. xylamidine was suppressed, it did not change after i.v. ketanserin. Neither i.c.v. nor i.v. PHE-induced pressor response was influenced by i.c.v. xylamidine pretreatment. These data suggest that the central 5-HT2 receptor may subserve pressor function in rats.

高血圧自然発症ラットにおける脳室内angiotensin II投与による血圧, およびvasopressinの変化に対するセロトニン作動神経系の関与

The purpose of the study is to investigate the role of the serotonergic nervous system in centrally administrated angiotensin II (A-II) mediated hemodynamic as well as vasopressin (AVP) responses. Eight-week-old male SHR and age-matched Wistar Kyoto rats (WKY) were used and the experiment was performed in the conscious state. In protocol 1, after resting observation of 30 minutes 10ng of A-II was given intracerebroventricularly (i.c.v.). This was followed by i.c.v. injection of 1 microgram of 5-HT2 receptor antagonist, xylamidine, 50 minutes later; then 10ng of i.c.v. A-II was repeated after 10 minutes (SHR: n = 7, WKY: n = 10). In protocol 2, plasma vasopressin (AVP) was measured in the following groups. In one group, 1.3ml of blood was sampled from the carotid cannula after resting observation, and the same amount of blood from an age-matched donor rat of the same strain was transfused immediately. Two hours later, 10ng of A-II was given i.c.v., and blood was sampled again after 1 minute (SHR: n = 7, WKY: n = 12). In another group, 1 microgram of xylamidine was given i.c.v. and was followed by 10ng of A-II 10 minutes later; then blood was collected after 1 minute (SHR: n = 8, WKY: n = 13). In protocol 1, resting MAP were 144 +/- 6mmHg in SHR and 99 +/- 2mmHg in WKY. I.c.v. A-II elicited a consistent pressor response in both SHR and WKY, but the response was significantly larger in SHR than that in WKY, +45 +/- 3 and +37 +/- 1mmHg, respectively. Xylamidine had no effect on MAP, and repeated A-II produced significant pressor responses. However, the responses were significantly smaller in both SHR (+36 +/- 3mmHg) and WKY (+25 +/- 1mmHg) as compared with those to initial A-II injection. In protocol 2, resting AVP were similar in SHR (1.5 +/- 0.2pg/ml) and in WKY (1.6 +/- 0.1pg/ml). However, after i.c.v. A-II injection, AVP became higher in SHR (131 +/- 14pg/ml) than in WKY (64 +/- 6pg/ml). AVP after A-II injection with xylamidine pretreatment were similar in SHR (48 +/- 6pg/ml) and in WKY (45 +/- 4pg/ml). Since the responses of both MAP and AVP to i.c.v. A-II were larger in SHR, and the responses were effectively suppressed by S2 receptor antagonists, the central serotonergic nervous system may play an important role in the hemodynamic as well as AVP responses to i.c.v. A-II administration.