Biomedical subjects

Steven L Bealer

Publications and source records attributed to Steven L Bealer.

10 recordsLinked to original sources

PubMed2007

Increased dietary sodium alters Fos expression in the lamina terminalis during intravenous angiotensin II infusion.

These studies examined the effects of increased dietary sodium on expression of Fos, the protein product of c-fos, in forebrain structures in the rat following intravenous infusion with angiotensin II (AngII). Animals were provided with either tap water (Tap) or isotonic saline solution (Iso) as their sole drinking fluid for 3-5 weeks prior to testing. Rats were then implanted with catheters in a femoral artery and vein. The following day, the conscious, unrestrained animals received iv infusion of either isotonic saline (Veh), AngII, or phenylephrine (Phen) for 2 h. Blood pressure and heart rate were monitored continuously throughout the procedure. Brains were subsequently processed for evaluation of Fos-like immunoreactivity (Fos-Li IR) in the organum vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO), and the median preoptic nucleus (MnPO). Fos-Li IR was significantly increased in the SFO and OVLT of animals consuming both Tap and Iso following AngII, but not Phen, compared to Veh infusions. Furthermore, Fos-Li IR in the MnPO was increased following AngII infusion in rats consuming a high sodium diet, but not in animals drinking Tap. These data suggest that increased dietary sodium sensitizes the MnPO neurons to excitatory input from brain areas responding to circulating AngII.

Angiotensin II↗

PubMed2006

Oxytocin receptor binding in the hypothalamus during gestation in rats.

Central oxytocin receptors (OTR) may be involved in adaptations of the brain oxytocin (OT) system during gestation, which are critical for systemic release of OT during parturition and lactation. We used quantitative autoradiography to determine changes in OTR binding in numerous brain sites during the course of gestation in the rat. Furthermore, to evaluate the importance of ovarian steroids in mediating pregnancy-related changes in OTR binding, we measured binding in ovariectomized animals treated with progesterone and/or estrogen, and in pregnant animals treated with exogenous progesterone during late gestation. We found that OTR binding was significantly increased in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by midgestation (day 15) compared with control. In addition, there was a further significant increase in OTR binding in these nuclei by late gestation (day 20). The bed nucleus of the stria terminalis (BNST) and the medial preoptic area (MPOA) also showed significant gestation-associated increases in OTR binding, which were similar during mid- and late pregnancy. Treatment with exogenous progesterone throughout pregnancy did not alter the increase in OTR binding characteristic of late gestation in any of these brain sites. Finally, estrogen treatment in ovariectomized animals resulted in increased OTR binding in the SON, BNST, and MPOA, but not the PVN. These data demonstrate that OTR binding in the hypothalamus is increased during mid- and late-gestation, compared with ovariectomized control animals, which may be mediated by increased estradiol.

Animals↗

PubMed2005

Increased dietary sodium enhances activation of neurons in the medullary cardiovascular pathway during acute sodium loading in the rat.

Increased sodium ingestion diminishes baroreflex-induced bradycardia in animals during acute sodium loading. These experiments studied effects of high sodium diet on activation of central nervous system sites associated with baroreflex activation and cardiovascular responses to hypernatremia during systemic sodium administration. Fos-like (Fos-Li) protein immunoreactivity was measured to estimate activation of neurons in the medullary baroreflex pathway (nucleus tractus solitarius (NTS), caudal ventrolateral medulla (CVLM), and rostral ventrolateral medulla (RVLM)), and in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) in male Sprague-Dawley rats consuming standard chow and either tap water (TAP) or isotonic saline (ISO) for 2-3 weeks. Fos-Li immunoreactivity in the PVN and SON was similar in rats consuming TAP and ISO infused with 0.6 M NaCl. However, there were significantly more Fos-Li positive cells in NTS and CVLM of animals consuming ISO and infused with 0.6 M NaCl than any other experimental group, while Fos-Li immunoreactivity was similar in the RVLM in all animals. In conclusion, these data demonstrate that activation of neurons in the NTS and CVLM was significantly enhanced by moderate sodium loading in animals consuming high dietary sodium. The increased basal activation of neurons in these medullary sites could account for decreased baroreflex-induced bradycardia observed during ingestion of a high salt diet and acute, moderate sodium loading.

Analysis of Variance↗

PubMed2005

Increased dietary sodium inhibits baroreflex-induced bradycardia during acute sodium loading.

The present study investigated the effects of increased dietary sodium on the modification of cardiac baroreflex responses induced by acute sodium loading. Changes in blood pressure and heart rate during intravenous phenylephrine and nitroprusside administration were compared using a four-parameter sigmoid logistic function before and after a 30-min infusion of 0.6 or 1.0 M NaCl in conscious male Sprague-Dawley rats consuming only tap water (Tap) or isotonic saline (Iso) for 2-3 wk. In Tap animals, infusion of 1.0 M NaCl increased the baroreflex-induced heart rate minimum, reduced heart rate range, and increased the operating blood pressure. In contrast, infusion of 0.6 M NaCl in Tap rats reduced both heart rate minimum and maximum. However, infusion of 0.6 M NaCl in Iso animals produced responses similar to that shown in Tap rats infused with 1.0 M NaCl. In addition, the decreased heart rate minimum in Tap rats after infusion of 0.6 M NaCl was prevented by intravenous administration of a vasopressin V1-receptor antagonist. Furthermore, cardiac parasympathetic responses were similar in Tap and Iso rats before and after 0.6 M NaCl infusion. However, in animals receiving intravenous atropine, 0.6 M NaCl decreased heart rate minimum and maximum in Tap but did not alter the response parameters in Iso rats. These results demonstrate that the facilitation of cardiac baroreflex responses normally observed during moderate sodium loading is mediated by vasopressin and that increased dietary sodium ingestion reverses this facilitation by reducing sympathetic nervous system withdrawal.

Animals↗

PubMed2004

Differential sensitivity of intranuclear and systemic oxytocin release to central noradrenergic receptor stimulation during mid- and late gestation in rats.

A number of changes occur in the oxytocin (OT) system during gestation, such as increases in hypothalamic OT mRNA, increased neural lobe and systemic OT, and morphological and electrophysiological changes in OT-containing magnocellular neurons, suggestive of altered neuronal sensitivity, which may be mediated by ovarian steroids. Because central norepinephrine (NE) and histamine (HA) are potent stimulators of OT release during parturition and lactation, the present study investigated the effects of central noradrenergic and histaminergic receptor activation on systemic (NE, HA) and intranuclear (NE) OT release in pregnant rats and in ovariectomized rats treated with ovarian steroids. Plasma OT levels in late gestation were significantly higher compared with all other groups, and neither adrenergic nor histaminergic receptor blockade decreased these elevated levels. Furthermore, the alpha-adrenergic agonist phenylephrine, but not histamine, stimulated systemic OT release to a significantly greater extent in late gestation than in midpregnant, ovariectomized, or steroid-treated females. Although basal extracellular OT levels in the paraventricular nucleus, as measured with microdialysis, were unchanged during pregnancy or steroid treatment, noradrenergic receptor stimulation of intranuclear OT release was significantly elevated in midgestation females compared with all other groups. These studies indicate that sensitivity of intranuclear and systemic OT release to noradrenergic receptor activation differentially varies during the course of gestation.

Adrenergic alpha-Agonists↗

PubMed2003

Angiotensin II-induced release of oxytocin: interaction with norepinephrine and role in lactation.

These studies examined the receptors involved in angiotensin II (Ang II) stimulated secretion of systemic oxytocin (OT) and the role of this peptide in release of OT during suckling. Plasma OT concentrations were measured following intracerebroventricular (icv) injection of vehicle, Ang II, or Ang II following pretreatment with a selective AT1 (Losartan) or AT2 (PD 123319) receptor antagonist. Furthermore, we measured Ang II-induced OT release during central alpha-adrenergic receptor blockade (phentolamine). Finally, plasma OT concentrations before and during suckling were evaluated following central administration of Ang II receptor antagonists. The increase in systemic OT following central Ang II was abolished by AT1 receptor blockade and inhibited by the AT2 receptor antagonist. Furthermore, pretreatment with phentolamine significantly diminished systemic OT release in response to icv Ang II. Finally, central Ang II receptor blockade did not alter the increase in circulating OT during suckling. These data demonstrate that Ang II evoked OT release is mediated through activation of both AT1 and AT2 receptors and suggest that a component of Ang II-induced OT stimulation is due to norepinephrine release. Furthermore, central angiotensin systems do not have a direct role in stimulating OT release during suckling.

Adrenergic alpha-Antagonists↗

PubMed2003

Peripheral hyperosmolality reduces cardiac baroreflex sensitivity.

The effects of acute increases in peripheral osmolality on cardiac baroreflex sensitivity were tested in conscious, unrestrained rats by fitting values for arterial blood pressure and heart rate during acute pressor and depressor responses to a four-parameter, sigmoid logistic function curve. Cardiac baroreceptor reflex function curves were produced before and following 30 min intravenous (i.v.) infusion of 2.5 M NaCl, an equipressor concentration of phenylephrine, isotonic saline, or 2.5 M NaCl following central administration of an angiotensin-converting enzyme (ACE) inhibitor. Hypertonic saline infusion increased blood pressure, reduced heart rate and baroreflex sensitivity (gain and range), and shifted the baroreflex function curve to a higher operating blood pressure. These effects were prevented or attenuated by prior central administration of an ACE inhibitor. Isotonic volume expansion did not alter baroreflex responses. Finally, phenylephrine produced similar changes in blood pressure but did not alter cardiac baroreflex responses. These data demonstrate that acute increases in peripheral osmolality and/or sodium decrease cardiac baroreflex sensitivity through generation of central angiotensin II, independent of changes in extracellular fluid volume and blood pressure.

Animals↗

PubMed2003

Central neurokinin 3 receptors increase systemic oxytocin release: interaction with norepinephrine.

Stimulation of central tachykinin receptors contributes to neuroendocrine functions of the hypothalamo-neurohypophyseal system. However, the specific role of each tachykinin receptor subtype has not been completely characterized. Specifically, while neurokinin 3 (NK3) receptor stimulation increases systemic vasopressin, the effects on oxytocin (OT) are not known. Therefore, the present studies investigated the effect of central NK3 receptor stimulation with senktide on release of systemic and central OT. Furthermore, since central NK3 receptors activate noradrenergic systems, which contribute to OT release, the effects of alpha-adrenergic receptor blockade on senktide-induced changes in OT release were evaluated. Female rats were implanted with a cannula in the third cerebral ventricle, and changes in plasma OT concentration determined before and following central administration of senktide in vehicle-treated rats, and animals following central administration of the alpha-adrenergic antagonist phentolamine. Other rats were implanted with microdialysis probes adjacent to the paraventricular nucleus (PVN), and dialysate and plasma OT concentrations were determined before and during administration of senktide through the dialysis probe. Central senktide increased systemic OT release, which was prevented by pretreatment with phentolamine. Furthermore, there was no detectable change in extracellular OT concentration in the PVN during dialysis administration of senktide. These data demonstrate that activation of central NK3 receptors stimulates systemic release of OT by activation of central noradrenergic systems, apparently without increasing intranuclear OT release in the PVN.

Adrenergic alpha-Antagonists↗

PubMed2002

Increased dietary sodium alters neural control of blood pressure during intravenous ANG II infusion.

Increased dietary sodium enhances both excitatory and inhibitory blood pressure responses to stimulation of the central sympathetic nervous system (SNS) centers. In addition, long-term (hours to days) administration of ANG II increases blood pressure by activation of the SNS. These studies investigated the effects of increased dietary sodium on SNS control of blood pressure during 0- to 24-h infusion of ANG II in conscious, male rats consuming either tap water or isotonic saline (Iso) for 2 to 3 wk. The SNS component (evaluated by ganglionic blockade with trimetaphan) of both control blood pressure and the pressor response to intravenous ANG II was reduced in Iso animals. Furthermore, although the pressor response to intravenous ANG II infusion was similar between groups, the baroreflex-induced bradycardia during the initial 6 h of ANG II infusion was significantly greater, whereas the tachycardia accompanying longer infusion periods was significantly attenuated in Iso animals. These data suggest that in normal rats increased dietary sodium enhances sympathoinhibitory responses during intravenous ANG II.

Angiotensin II↗

PubMed2002

Systemic angiotensin II alters intrinsic heart rate through central mechanisms.

Angiotensin II (ang II)-induced increases in intrinsic heart rate (IHR), and the resulting tachycardia, may contribute to development of renal hypertension. Whether circulating ang II affects the cardiac pacemaker through peripheral mechanisms or through actions in the central nervous system (CNS) has not been directly tested. These studies determined the role of a central site of ang II action, the tissue surrounding the anteroventral third ventricle (AV3V), in increased IHR induced by systemic ang II. Blood pressure and heart rate were measured in male rats with lesions of the AV3V region and in control-operated animals during i.v. infusion (3 h) of ang II, norepinephrine, or vehicle. IHR was evaluated at the end of the infusion period. Systemic ang II increased blood pressure equally in both experimental groups. However, heart rate was reduced only in animals with AV3V lesions. Furthermore, ang II increased IHR only in control-operated rats. Changes in blood pressure, heart rate, and IHR in response to norepinephrine infusion were similar between animals with AV3V lesions and control-operated rats. These data demonstrate that systemic ang II mediates IHR through actions in the CNS, specifically the AV3V region.

Angiotensin II↗