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Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois 60513
Central
administration of serotonergic 5-HT1A receptor agonists
delays the reflex sympatholytic response to severe hemorrhage in
conscious rats. To determine the region where 5-HT1A
receptor agonists act to mediate this response, recovery of mean
arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve
activity (RSNA) was compared in hemorrhaged rats after injection of the selective 5-HT1A agonist,
(+)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), in
various regions of the cerebroventricular system or the systemic
circulation. Three minutes after injection of 8-OH-DPAT (48 nmol/kg),
MAP and RSNA were higher in hemorrhaged rats given drug in the fourth
ventricle (94 ± 5 mmHg, 82 ± 18% of baseline) or the
systemic circulation (90 ± 4 mmHg, 113 ± 15% of baseline)
than in rats given drug in the Aqueduct of Sylvius (63 ± 4 mmHg,
27 ± 11% of baseline), the lateral ventricle (42 ± 3 mmHg,
8 ± 18% of baseline), or in rats given saline in various brain
regions (47 ± 5 mmHg, 42 ± 10% of baseline). A
lower-dose injection of 8-OH-DPAT (10 nmol/kg) also accelerated the
recovery of MAP and RSNA in hemorrhaged rats when given in the fourth
ventricle (94 ± 26 mmHg, 72 ± 33% of baseline 3 min after
injection) but not the systemic circulation (46 ± 4 mmHg,
25 ± 30% of baseline). These data indicate that 8-OH-DPAT acts
on receptors in the hindbrain to reverse the sympatholytic response to
hemorrhage in conscious rats.
(+)-8-hydroxy-2-(di-n-propylamino)tetralin; 5-hydroxytryptamine type 1A
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