The spleen is required for 5-HT1A receptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat

The 5-HT1A receptor agonist, 8- OH-DPAT, increases whole body venous tone (mean circulatory filling pressure; MCFP), and attenuates metabolic acidosis in a rat model of unresuscitated hemorrhagic shock. To determine whether improved acid-base balance was associated with sympathetic activation and venous constriction, MCFP, sympathetic activity (SA), and blood gases were compared in hemorrhaged rats following administration of 5-HT1A receptor agonist 8-OH-DPAT, the arterial vasoconstrictor arginine vasopressin (AVP), or saline. To further determine whether protection of acid-base balance was dependent on splenic contraction and blood mobilization, central venous pressure (CVP), MCFP, and blood gases were determined during hemorrhage and subsequent 8-OH-DPAT-administration in rats subjected to real or sham splenectomy. Subjects were hemorrhaged to an arterial pressure of 50 mmHg for 25 min and subsequently were treated with 8-OH-DPAT (30 nmol/kg iv), AVP titrated to match the pressor effect of 8-OH-DPAT (∼2 ng/min iv), or infusion of normal saline. 8-OH-DPAT increased MAP, CVP, MCFP, and SA, and decreased lactate accumulation. AVP did not affect CVP or SA, but raised MCFP slightly to a level intermediate between 8-OH-DPAT- and saline-treated rats. Infusion of AVP also produced a modest protection against metabolic acidosis. Splenectomy prevented the rise in CVP, MCFP, and protection against metabolic acidosis produced by 8-OH-DPAT but had no effect on the immediate pressor response to the drug. Together, the data indicate that 8-OH-DPAT produces a pattern of cardiovascular responses consistent with a sympathetic-mediated venoconstriction that is, in part, responsible for the drug's beneficial effect on acid-base balance. Moreover, blood mobilization stimulated by the spleen is required for the beneficial effects of 8-OH-DPAT

5-Hydroxytryptamine 1A receptors in the paraventricular nucleus of the hypothalamus mediate oxytocin and adrenocorticotropin hormone release and some behavioral components of the serotonin syndrome

Neuroendocrine responses to administration of serotonin releasing agents or 5-hydroxytryptamine (5-HT) 1A receptor agonists have been used as an index of serotonin receptor function in patients with depression and other mood disorders. However, the receptor population that mediates these responses has not been clearly identified. We tested the hypothesis that 5-HT1A receptors in the paraventricular nucleus of the hypothalamus (PVN) mediate the release of adrenocorticotropin hormone (ACTH) and oxytocin after administration of a selective 5-HT1A agonist in conscious rats. Low-dose infusion (1 nmol/100 nl/side) of the selective 5-HT1A antagonist, WAY100635 (WAY; [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl)-N-( 2- pyridinyl)cyclohexanecarboxamidetrihydrochloride), into the PVN blocked the rise in ACTH and oxytocin stimulated by low-dose (30 nmol/kg) i.v. administration of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 274 +/- 53 versus 70 +/- 20 pg/ ml, P < 0.01 for ACTH and 10.7 +/- 3.4 versus 4.6 +/- 0.7 pg/ml, P < 0.05 for oxytocin after saline or WAY pretreatment, respectively). WAY did not influence the bradycardic effect of 8-OH-DPAT (-56 +/- 7 versus -54 +/- 6 beats per minute after saline or WAY). 8-OH-DPAT treatment also elicited locomotor activation followed by hind limb abduction and flat body posture. Surprisingly, WAY attenuated some aspects of locomotor activation and reduced the duration of hind limb abduction elicited by the agonist (5.1 +/- 0.9 versus 0.3 +/- 0.3 min for saline- or WAY-treated rats). These data indicate that 5-HT1A receptor stimulation in the PVN mediates the characteristic neuroendocrine response to serotonin agonist challenge. Moreover, they provide the first evidence that aspects of the behavioral serotonin syndrome are mediated by forebrain hypothalamic receptors

Selective Impairment Of Central Mediation Of Baroreflex In Anesthetized Young Adult Fischer 344 Rats After Chronic Intermittent Hypoxia

Baroreflex control of heart rate (HR) is impaired after chronic intermittent hypoxia (CIH). However, the location and nature of this response remain unclear. We examined baroreceptor afferent, vagal efferent, and central components of the baroreflex circuitry. Fischer 344 (F344) rats were exposed to room air (RA) or CIH for 35-50 days and were then anesthetized with isoflurane, ventilated, and catheterized for measurement of mean arterial blood pressure (MAP) and HR. Baroreceptor function was characterized by measuring percent changes of integrated aortic depressor nerve (ADN) activity (Int ADNA) relative to the baseline value in response to sodium nitroprusside- and phenylephrine-induced changes in MAP. Data were fitted to a sigmoid logistic function curve. HR responses to electrical stimulation of the left ADN and the right vagus nerve were assessed under ketamine-acepromazine anesthesia. Compared with RA controls, CIH significantly increased maximum baroreceptor gain or maximum slope, maximum Int ADNA, and Int ADNA range (maximum - minimum Int ADNA), whereas other parameters of the logistic function were unchanged. In addition, CIH increased the maximum amplitude of bradycardic response to vagal efferent stimulation and decreased the time from stimulus onset to peak response. In contrast, CIH significantly reduced the maximum amplitude of bradycardic response to left ADN stimulation and increased the time from stimulus onset to peak response. Therefore, CIH decreased central mediation of the baroreflex but augmented baroreceptor afferent function and vagal efferent control of HR