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Articles in PresS, published online ahead of print November 7, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00478.2002
Submitted on August 12, 2002
Accepted on November 5, 2002
1 Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA
* To whom correspondence should be addressed. E-mail: kscrogi{at}lumc.edu.
Central administration of serotonergic 5-HT1A receptor agonists delay 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) were compared in hemorrhaged rats following injection of the selective 5-HT1A agonist, 8-OH-DPAT, into various regions of the cerebroventricular system or the systemic circulation. Three min after injection of 8-OH-DPAT (48 nmol/kg), MAP and RSNA were higher in rats given drug into the 4th ventricle (94 ± 5 mmHg, 82 ± 18 %baseline) or the systemic circulation (90 ± 4 mmHg, 113 ± 15 %baseline) than in rats given drug into the Aqueduct of Sylvius (63 ± 4 mmHg, 27 ± 11 % baseline), the lateral ventricle (42 ± 3 mmHg, -8 ± 18 % baseline) or in rats given saline into various brain regions (47 ± 5 mmHg, -42 ± 10 %baseline). A lower dose injection of 8-OH-DPAT (10 nmol/kg) also accelerate the recovery of MAP and RSNA in hemorrhaged rats when given into the 4th ventricle (94 ± 26 mmHg, 72 ± 33 %baseline 3 min after injection), but not the systemic circulation (46 ± 4 mmHg, -25 ± 30 %baseline). These data indicate that 8-OH-DPAT acts on receptors in the hindbrain to reverse the sympatholytic response to hemorrhage in conscious rats.
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