TY - JOUR
T1 - Methysergide delays the decompensatory responses to severe hemorrhage by activating 5-HT(1A) receptors
AU - Scrogin, Karie E.
AU - Johnson, Alan Kim
AU - Brooks, Virginia L.
PY - 2000
Y1 - 2000
N2 - Central administration of the serotonin receptor ligand methysergide delays the decompensatory response to hypotensive hemorrhage. This study was performed to determine the receptor subtype that mediates this effect. Lateral ventricular (LV) injection of methysergide (40 μg) delayed the hypotensive, bradycardic, and sympathoinhibitory responses to blood withdrawal (1.26 ml/min) in conscious rats. The response was quantified, in part, as the blood volume withdrawal that produced a 40-mmHg fall in blood pressure. The delayed hypotensive response produced by methysergide (8.2 ± 0.2 vs. 5.6 ± 0.2 ml, P < 0.01) was reversed by the 5-hydroxytryptamine (HT)(1A) antagonist WAY-100635 (30 μg iv: 6.7 ± 0.4 ml, P < 0.01; 100 μg iv: 5.6 ± 0.1 ml, P < 0.01). LV injection of the 5-HT(1A) agonist (+)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) also delayed the hypotensive (10 μg: 8.6 ± 0.3, P < 0.01; 20 μg: 9.2 ± 0.3 ml, P < 0.01), bradycardic, and sympatho-inhibitory responses to hemorrhage. WAY-100635 (10 μg iv) completely reversed the effects of 8-OH-DPAT (20 μg: 5.4 ± 0.3 ml). Neither selective blockade of 5-HT2 receptors nor stimulation of 5-HT(1B/1D) receptors had any effect on hemorrhage responses. These data indicate that methysergide stimulates 5-HT(1A) receptors to delay the decompensatory responses to hemorrhage.
AB - Central administration of the serotonin receptor ligand methysergide delays the decompensatory response to hypotensive hemorrhage. This study was performed to determine the receptor subtype that mediates this effect. Lateral ventricular (LV) injection of methysergide (40 μg) delayed the hypotensive, bradycardic, and sympathoinhibitory responses to blood withdrawal (1.26 ml/min) in conscious rats. The response was quantified, in part, as the blood volume withdrawal that produced a 40-mmHg fall in blood pressure. The delayed hypotensive response produced by methysergide (8.2 ± 0.2 vs. 5.6 ± 0.2 ml, P < 0.01) was reversed by the 5-hydroxytryptamine (HT)(1A) antagonist WAY-100635 (30 μg iv: 6.7 ± 0.4 ml, P < 0.01; 100 μg iv: 5.6 ± 0.1 ml, P < 0.01). LV injection of the 5-HT(1A) agonist (+)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) also delayed the hypotensive (10 μg: 8.6 ± 0.3, P < 0.01; 20 μg: 9.2 ± 0.3 ml, P < 0.01), bradycardic, and sympatho-inhibitory responses to hemorrhage. WAY-100635 (10 μg iv) completely reversed the effects of 8-OH-DPAT (20 μg: 5.4 ± 0.3 ml). Neither selective blockade of 5-HT2 receptors nor stimulation of 5-HT(1B/1D) receptors had any effect on hemorrhage responses. These data indicate that methysergide stimulates 5-HT(1A) receptors to delay the decompensatory responses to hemorrhage.
KW - Blood pressure
KW - Renal sympathetic activity
KW - Serotonin
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U2 - 10.1152/ajpregu.2000.279.5.r1776
DO - 10.1152/ajpregu.2000.279.5.r1776
M3 - Article
C2 - 11049861
AN - SCOPUS:0033672557
SN - 0363-6119
VL - 279
SP - R1776-R1786
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 5 48-5
ER -