Abstract
Background: We previously reported that chronic inhibition of nitric oxide synthesis by administration of N(ω)-nitro-L-arginine methyl ester (L- NAME) causes microvascular hyperreactivity to 5-hydroxytryptamine (5-HT) and vascular structural changes in pigs in vivo. In the present study, we investigated the relative contributions of 5-HT receptor subtypes to microvascular hyperreactivity in this animal model. Methods and Results: Coronary vasomotor response was studied in 16 pigs treated with oral L-NAME for 4 weeks (L group) and in 11 control pigs (C group). Intracoronary administration of 5-HT at 30 μg/kg decreased coronary blood flow (CBF) in the two groups. The decrease in CBF by 5-HT was greater (P<.01) in the L group than in the C group. The decrease in CBF by 5-HT in the C group was blocked completely by pretreatment with ketanserin, a 5-HT2 antagonist. In contrast, the augmented decrease in CBF by 5-HT in the L group was only partly inhibited by ketanserin alone and was blocked completely by ketanserin and methiothepin, a 5-HT1/5-HT2 antagonist. The decrease in CBF caused by prostaglandin F(2α) and the increase in CBF caused by nitroglycerin were comparable between the two groups and were not affected by the 5-HT antagonists. Conclusions: These results suggest that the 5-HT-induced microvascular hyperreactivity may be mediated by relative changes in affinity for 5-HT receptors or de novo expression of 5-HT1 receptors in microvascular smooth muscle cells in our animal model.
| Original language | English |
|---|---|
| Pages (from-to) | 182-189 |
| Number of pages | 8 |
| Journal | Circulation |
| Volume | 94 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 1 1996 |
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All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
Altered serotonin receptor subtypes mediate coronary microvascular hyperreactivity in pigs with chronic inhibition of nitric oxide synthesis. / Kadokami, Toshiaki; Egashira, Kensuke; Kuwata, Kouichi; Fukumoto, Yoshihiro; Kozai, Toshiyuki; Yasutake, Hiroshi; Kuga, Takeshi; Shimokawa, Hiroaki; Sueishi, Katsuo; Takeshita, Akira.
In: Circulation, Vol. 94, No. 2, 01.01.1996, p. 182-189.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Altered serotonin receptor subtypes mediate coronary microvascular hyperreactivity in pigs with chronic inhibition of nitric oxide synthesis
AU - Kadokami, Toshiaki
AU - Egashira, Kensuke
AU - Kuwata, Kouichi
AU - Fukumoto, Yoshihiro
AU - Kozai, Toshiyuki
AU - Yasutake, Hiroshi
AU - Kuga, Takeshi
AU - Shimokawa, Hiroaki
AU - Sueishi, Katsuo
AU - Takeshita, Akira
PY - 1996/1/1
Y1 - 1996/1/1
N2 - Background: We previously reported that chronic inhibition of nitric oxide synthesis by administration of N(ω)-nitro-L-arginine methyl ester (L- NAME) causes microvascular hyperreactivity to 5-hydroxytryptamine (5-HT) and vascular structural changes in pigs in vivo. In the present study, we investigated the relative contributions of 5-HT receptor subtypes to microvascular hyperreactivity in this animal model. Methods and Results: Coronary vasomotor response was studied in 16 pigs treated with oral L-NAME for 4 weeks (L group) and in 11 control pigs (C group). Intracoronary administration of 5-HT at 30 μg/kg decreased coronary blood flow (CBF) in the two groups. The decrease in CBF by 5-HT was greater (P<.01) in the L group than in the C group. The decrease in CBF by 5-HT in the C group was blocked completely by pretreatment with ketanserin, a 5-HT2 antagonist. In contrast, the augmented decrease in CBF by 5-HT in the L group was only partly inhibited by ketanserin alone and was blocked completely by ketanserin and methiothepin, a 5-HT1/5-HT2 antagonist. The decrease in CBF caused by prostaglandin F(2α) and the increase in CBF caused by nitroglycerin were comparable between the two groups and were not affected by the 5-HT antagonists. Conclusions: These results suggest that the 5-HT-induced microvascular hyperreactivity may be mediated by relative changes in affinity for 5-HT receptors or de novo expression of 5-HT1 receptors in microvascular smooth muscle cells in our animal model.
AB - Background: We previously reported that chronic inhibition of nitric oxide synthesis by administration of N(ω)-nitro-L-arginine methyl ester (L- NAME) causes microvascular hyperreactivity to 5-hydroxytryptamine (5-HT) and vascular structural changes in pigs in vivo. In the present study, we investigated the relative contributions of 5-HT receptor subtypes to microvascular hyperreactivity in this animal model. Methods and Results: Coronary vasomotor response was studied in 16 pigs treated with oral L-NAME for 4 weeks (L group) and in 11 control pigs (C group). Intracoronary administration of 5-HT at 30 μg/kg decreased coronary blood flow (CBF) in the two groups. The decrease in CBF by 5-HT was greater (P<.01) in the L group than in the C group. The decrease in CBF by 5-HT in the C group was blocked completely by pretreatment with ketanserin, a 5-HT2 antagonist. In contrast, the augmented decrease in CBF by 5-HT in the L group was only partly inhibited by ketanserin alone and was blocked completely by ketanserin and methiothepin, a 5-HT1/5-HT2 antagonist. The decrease in CBF caused by prostaglandin F(2α) and the increase in CBF caused by nitroglycerin were comparable between the two groups and were not affected by the 5-HT antagonists. Conclusions: These results suggest that the 5-HT-induced microvascular hyperreactivity may be mediated by relative changes in affinity for 5-HT receptors or de novo expression of 5-HT1 receptors in microvascular smooth muscle cells in our animal model.
UR - http://www.scopus.com/inward/record.url?scp=8944237009&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8944237009&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.94.2.182
DO - 10.1161/01.CIR.94.2.182
M3 - Article
C2 - 8674177
AN - SCOPUS:8944237009
VL - 94
SP - 182
EP - 189
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 2
ER -