Information about reprints can be found online at: Reprints: document. Permissions and Rights Que... more Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer this process is available in the click Request Permissions in the middle column of the Web page under Services. Further information about Office. Once the online version of the published article for which permission is being requested is located, can be obtained via RightsLink, a service of the Copyright Clearance Center, not the EditorialHypertensionin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on March 4,
American Journal of Physiology-Endocrinology and Metabolism
Peripheral osmoreceptors monitor dietary NaCl and modify central nervous system and renal sympath... more Peripheral osmoreceptors monitor dietary NaCl and modify central nervous system and renal sympathetic nervous system activity accordingly. Experimental evidence suggests that these responses are dependent on the hepatic nerves. Peripheral osmoreceptors also modify arginine vasopressin (AVP) secretion. However, although hepatic denervation reportedly blunts activation of both supraoptic and paraventricular hypothalamic neurons after intraportal NaCl infusion, the role of the hepatic nerves in the AVP release has not been directly examined. The present study tests the hypothesis that the hepatic nerves modify AVP release in response to intragastric NaCl infusion. Wistar-Kyoto rats (WKY) received either hepatic denervation or a sham operation. Intragastric NaCl infusion significantly elevated plasma AVP in both sham-operated WKY and hepatic-denervated WKY, and the responses were not different between these groups. Second, previous studies suggest that both AVP secretion and baroreflexe...
To regulate blood pressure, the brain controls circulating hormones, which influence the brain by... more To regulate blood pressure, the brain controls circulating hormones, which influence the brain by binding to brain neurons that lie outside the blood-brain barrier. Recent work has demonstrated that "cardiovascular" hormones are synthesized and released in the brain as neurotransmitters/neuromodulators and can, in some cases, signal through the blood-brain barrier. The renin-angiotensin system is a prototype for these newly appreciated mechanisms. The brain's intrinsic renin-angiotensin system plays an important role in blood pressure control. Angiotensin II in brain neurons affects other neurons both through activation of angiotensin receptors and via generation of nitric oxide and reactive oxygen molecules. Similarly, angiotensin in blood vessels activates endothelial nitric oxide, which can diffuse across the blood-brain barrier and thereby alter neuronal activity in cardiovascular control nuclei. The relative importance of these mechanisms to blood pressure control remains to be fully elucidated.
American Journal of Physiology Regulatory Integrative and Comparative Physiology, May 1, 1998
We have recently reported that an acute intragastric hypertonic saline load increases plasma argi... more We have recently reported that an acute intragastric hypertonic saline load increases plasma arginine vasopressin (PAVP) and Fos immunoreactivity in several central nuclei, including the supraoptic nucleus (SON), paraventricular nucleus (PVN), nucleus of the solitary tract (NTS), area postrema (AP), and lateral parabrachial nucleus (LPBN). We hypothesized that these responses are mediated by stimulation of peripheral osmoreceptors with splanchnic and/or vagal afferent projections. To test this hypothesis, we examined the effect of bilateral subdiaphragmatic vagotomy and bilateral splanchnic denervation on the PAVP and Fos immunoreactivity responses to intragastric hypertonic saline infusion in awake rats. Compared with responses in sham rats, Fos immunoreactivity responses were significantly reduced in vagotomized rats in the AP, SON, and PVN, whereas normal Fos levels were observed in the LPBN. However, vagotomized rats exhibited a normal increase in PAVP. Splanchnic-denervated rats also exhibited similar changes in PAVP in response to intragastric hypertonic saline compared with sham-denervated rats, and no differences were observed in Fos immunoreactivity in the LPBN, SON, and PVN compared with sham rats. However, splanchnic-denervated rats were observed to have significantly lower Fos staining in the NTS and AP compared with sham rats. The inability of splanchnic or vagal denervation alone to block the PAVP response to intragastric hypertonic saline suggests that either peripheral osmoreceptors project via both splanchnic and vagal afferents to mediate AVP release or that the observed response of PAVP is due to the activation of central osmoreceptors in the absence of measurable changes in plasma osmolality.
MS/MS is a widely used method for proteome-wide analysis of protein expression and PTMs. The thou... more MS/MS is a widely used method for proteome-wide analysis of protein expression and PTMs. The thousands of MS/MS spectra produced from a single experiment pose a major challenge for downstream analysis. Standard programs, such as MASCOT, provide peptide assignments for many of the spectra, including identification of PTM sites, but these results are plagued by false-positive identifications. In phosphoproteomic experiments, only a single peptide assignment is typically available to support identification of each phosphorylation site, and hence minimizing false positives is critical. Thus, tedious manual validation is often required to increase confidence in the spectral assignments. We have developed phoMSVal, an open-source platform for managing MS/MS data and automatically validating identified phosphopeptides. We tested five classification algorithms with 17 extracted features to separate correct peptide assignments from incorrect ones using over 2600 manually curated spectra. The naïve Bayes algorithm was among the best classifiers with an AUC value of 97% and PPV of 97% for phosphotyrosine data. This classifier required only three features to achieve a 76% decrease in false positives as compared with MASCOT while retaining 97% of true positives. This algorithm was able to classify an independent phosphoserine/threonine data set with AUC value of 93% and PPV of 91%, demonstrating the applicability of this method for all types of phospho-MS/MS data. PhoMSVal is available at http://csbi.ltdk.helsinki.fi/phomsval.
Although experimental evidence supports peripheral osmoreceptor modulation of arginine vasopressi... more Although experimental evidence supports peripheral osmoreceptor modulation of arginine vasopressin (AVP) release, a local osmotic signal required for osmoreceptor activation has yet to be identified using physiological sodium loads. Additionally, the central pathway involved in peripheral control of AVP has not been clearly established. Experiments were conducted to examine the effect of intragastric saline on portal venous osmolarity, plasma AVP (P(AVP)), and Fos immunoreactivity. In anesthetized rats, intragastric infusion (2.9 ml) of hypertonic (600 mosM) saline significantly increased portal venous osmolarity while systemic blood osmolarity remained constant. In conscious rats, intragastric hypertonic saline significantly elevated P(AVP) (3.6 +/- 1.3 to 5.8 +/- 1.9 pg/ml), whereas no changes were observed in plasma osmolarity in either the isotonic (296.2 +/- 1.4 to 297.6 +/- 1.1 mosM) or hypertonic (291.7 +/- 1.7 to 291.4 +/- 1.8 mosM) group. Finally, intragastric hypertonic saline significantly increased Fos immunoreactivity in the nucleus of the solitary tract (NTS), area postrema (AP), lateral parabrachial nucleus (LPBN), supraoptic nucleus (SON), and paraventricular nucleus (PVN). These results indicate that intragastric hypertonic saline produces a portal venous osmotic signal that triggers peripheral osmoreceptors to stimulate AVP release while activating the NTS, AP, and LPBN in addition to the SON and PVN.
Hypertension is a major health problem that significantly contributes to heart disease and stroke... more Hypertension is a major health problem that significantly contributes to heart disease and stroke. While most studies of hypertension have focused on men, women also experience significant hypertension-related morbidity and mortality. However, the incidence of hypertension and cardiovascular disease is significantly lower in premenopausal women compared with men until the onset of menopause, at which time cardiovascular disease incidence increases dramatically in women and eventually approaches that in men. These observations indicate that the loss of estrogen contributes to menopause-related increases in blood pressure and cardiovascular disease, and suggest that the use of estrogen hormone replacement therapy could decrease the incidence of cardiovascular disease in postmenopausal women. However, new findings from the Women's Health Initiative study suggest that estrogen therapy has few positive benefits and some significant negative effects on the health of postmenopausal women, and these data have caused many to abandon long-term estrogen replacement therapy. Conversely, numerous clinical and basic research studies indicate that estrogen replacement therapy beneficially reduces blood pressure, thereby decreasing the incidence of hypertension and cardiovascular disease. Further, several of these studies suggest that one means by which estrogen lowers blood pressure is by decreasing sympathetic nervous system activity. This review examines the evidence supporting estrogen's ability to modulate sympathetic nervous system tone and thereby decrease arterial pressure.
International Journal of Sport Psychology, Sep 1, 2012
ABSTRACT The Contextual Sensation Seeking Questionnaire (CSSQ-S) was developed to measure pattern... more ABSTRACT The Contextual Sensation Seeking Questionnaire (CSSQ-S) was developed to measure patterns of sensation-seeking behaviours in skiing and snowboarding. We conducted three studies supporting several aspects of its validity. First, using a focus group (n = 4) we generated items representative of sensation seeking in skiing and explored the factor structure in a sample of skiers (n1 = 220). Second, we confirmed the factor structure using data from an independent cohort (n2 = 530). Finally, we provide evidence for criterion-relevance and applied utility of CSSQ-S scores by demonstrating positive relationships between scores and self-reported injury. CSSQ-S scores explained greater variance (n1 = 217, β = .358, p < .001) in injury prevalence than an established assessment tool (Zuckerman’s Impulsive-Sensation Seeking scale). In summary, the CSSQ-S represents a psychometrically promising measure of contextual sensation seeking and may be used to explore factors associated with risk-taking in skiing and snowboarding.
Several lines of evidence suggest that peripheral osmoreceptors respond to alterations in dietary... more Several lines of evidence suggest that peripheral osmoreceptors respond to alterations in dietary NaCl by adjusting renal sympathetic nerve activity, but the impact of this reflex on the long-term regulation of mean arterial pressure (MAP) remains unclear. The present study tested the hypothesis that denervation of peripheral osmoreceptors elevates arterial pressure and induces NaCl-sensitive hypertension in normotensive rats. Hepatic denervated
P300 amplitude predicts substance use or disorder by age 21. Earlier- versus later-onset substanc... more P300 amplitude predicts substance use or disorder by age 21. Earlier- versus later-onset substance disorders may reflect different levels of an externalizing psychopathology dimension. P300 in adolescence may not be as strongly related to later-onset substance problems as it is to earlier-onset ones. In the present study, visual P300 amplitude was measured at age 17 in a community-representative sample of young men. Substance and externalizing disorders were assessed at approximately ages 17, 20, and 24. Earlier-onset (by age 20) substance disorder was associated with higher rates of externalizing disorders than were later-onset problems. P300 amplitude was reduced in subjects with earlier-onset substance disorders, relative to later-onset and disorder-free subjects. Amplitude was also reduced in subjects with an externalizing disorder but no substance disorder. Earlier-onset subjects had reduced P300, even in the absence of an externalizing disorder. The results could not be attributed to a concurrent disorder or to recent substance use at the time of the P300 recording. The findings are consistent with P300 indexing an externalizing spectrum. Earlier-onset substance disorders are more strongly related to P300 and externalizing than are later-onset problems.
Information about reprints can be found online at: Reprints: document. Permissions and Rights Que... more Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer this process is available in the click Request Permissions in the middle column of the Web page under Services. Further information about Office. Once the online version of the published article for which permission is being requested is located, can be obtained via RightsLink, a service of the Copyright Clearance Center, not the EditorialHypertensionin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on March 4,
American Journal of Physiology-Endocrinology and Metabolism
Peripheral osmoreceptors monitor dietary NaCl and modify central nervous system and renal sympath... more Peripheral osmoreceptors monitor dietary NaCl and modify central nervous system and renal sympathetic nervous system activity accordingly. Experimental evidence suggests that these responses are dependent on the hepatic nerves. Peripheral osmoreceptors also modify arginine vasopressin (AVP) secretion. However, although hepatic denervation reportedly blunts activation of both supraoptic and paraventricular hypothalamic neurons after intraportal NaCl infusion, the role of the hepatic nerves in the AVP release has not been directly examined. The present study tests the hypothesis that the hepatic nerves modify AVP release in response to intragastric NaCl infusion. Wistar-Kyoto rats (WKY) received either hepatic denervation or a sham operation. Intragastric NaCl infusion significantly elevated plasma AVP in both sham-operated WKY and hepatic-denervated WKY, and the responses were not different between these groups. Second, previous studies suggest that both AVP secretion and baroreflexe...
To regulate blood pressure, the brain controls circulating hormones, which influence the brain by... more To regulate blood pressure, the brain controls circulating hormones, which influence the brain by binding to brain neurons that lie outside the blood-brain barrier. Recent work has demonstrated that "cardiovascular" hormones are synthesized and released in the brain as neurotransmitters/neuromodulators and can, in some cases, signal through the blood-brain barrier. The renin-angiotensin system is a prototype for these newly appreciated mechanisms. The brain's intrinsic renin-angiotensin system plays an important role in blood pressure control. Angiotensin II in brain neurons affects other neurons both through activation of angiotensin receptors and via generation of nitric oxide and reactive oxygen molecules. Similarly, angiotensin in blood vessels activates endothelial nitric oxide, which can diffuse across the blood-brain barrier and thereby alter neuronal activity in cardiovascular control nuclei. The relative importance of these mechanisms to blood pressure control remains to be fully elucidated.
American Journal of Physiology Regulatory Integrative and Comparative Physiology, May 1, 1998
We have recently reported that an acute intragastric hypertonic saline load increases plasma argi... more We have recently reported that an acute intragastric hypertonic saline load increases plasma arginine vasopressin (PAVP) and Fos immunoreactivity in several central nuclei, including the supraoptic nucleus (SON), paraventricular nucleus (PVN), nucleus of the solitary tract (NTS), area postrema (AP), and lateral parabrachial nucleus (LPBN). We hypothesized that these responses are mediated by stimulation of peripheral osmoreceptors with splanchnic and/or vagal afferent projections. To test this hypothesis, we examined the effect of bilateral subdiaphragmatic vagotomy and bilateral splanchnic denervation on the PAVP and Fos immunoreactivity responses to intragastric hypertonic saline infusion in awake rats. Compared with responses in sham rats, Fos immunoreactivity responses were significantly reduced in vagotomized rats in the AP, SON, and PVN, whereas normal Fos levels were observed in the LPBN. However, vagotomized rats exhibited a normal increase in PAVP. Splanchnic-denervated rats also exhibited similar changes in PAVP in response to intragastric hypertonic saline compared with sham-denervated rats, and no differences were observed in Fos immunoreactivity in the LPBN, SON, and PVN compared with sham rats. However, splanchnic-denervated rats were observed to have significantly lower Fos staining in the NTS and AP compared with sham rats. The inability of splanchnic or vagal denervation alone to block the PAVP response to intragastric hypertonic saline suggests that either peripheral osmoreceptors project via both splanchnic and vagal afferents to mediate AVP release or that the observed response of PAVP is due to the activation of central osmoreceptors in the absence of measurable changes in plasma osmolality.
MS/MS is a widely used method for proteome-wide analysis of protein expression and PTMs. The thou... more MS/MS is a widely used method for proteome-wide analysis of protein expression and PTMs. The thousands of MS/MS spectra produced from a single experiment pose a major challenge for downstream analysis. Standard programs, such as MASCOT, provide peptide assignments for many of the spectra, including identification of PTM sites, but these results are plagued by false-positive identifications. In phosphoproteomic experiments, only a single peptide assignment is typically available to support identification of each phosphorylation site, and hence minimizing false positives is critical. Thus, tedious manual validation is often required to increase confidence in the spectral assignments. We have developed phoMSVal, an open-source platform for managing MS/MS data and automatically validating identified phosphopeptides. We tested five classification algorithms with 17 extracted features to separate correct peptide assignments from incorrect ones using over 2600 manually curated spectra. The naïve Bayes algorithm was among the best classifiers with an AUC value of 97% and PPV of 97% for phosphotyrosine data. This classifier required only three features to achieve a 76% decrease in false positives as compared with MASCOT while retaining 97% of true positives. This algorithm was able to classify an independent phosphoserine/threonine data set with AUC value of 93% and PPV of 91%, demonstrating the applicability of this method for all types of phospho-MS/MS data. PhoMSVal is available at http://csbi.ltdk.helsinki.fi/phomsval.
Although experimental evidence supports peripheral osmoreceptor modulation of arginine vasopressi... more Although experimental evidence supports peripheral osmoreceptor modulation of arginine vasopressin (AVP) release, a local osmotic signal required for osmoreceptor activation has yet to be identified using physiological sodium loads. Additionally, the central pathway involved in peripheral control of AVP has not been clearly established. Experiments were conducted to examine the effect of intragastric saline on portal venous osmolarity, plasma AVP (P(AVP)), and Fos immunoreactivity. In anesthetized rats, intragastric infusion (2.9 ml) of hypertonic (600 mosM) saline significantly increased portal venous osmolarity while systemic blood osmolarity remained constant. In conscious rats, intragastric hypertonic saline significantly elevated P(AVP) (3.6 +/- 1.3 to 5.8 +/- 1.9 pg/ml), whereas no changes were observed in plasma osmolarity in either the isotonic (296.2 +/- 1.4 to 297.6 +/- 1.1 mosM) or hypertonic (291.7 +/- 1.7 to 291.4 +/- 1.8 mosM) group. Finally, intragastric hypertonic saline significantly increased Fos immunoreactivity in the nucleus of the solitary tract (NTS), area postrema (AP), lateral parabrachial nucleus (LPBN), supraoptic nucleus (SON), and paraventricular nucleus (PVN). These results indicate that intragastric hypertonic saline produces a portal venous osmotic signal that triggers peripheral osmoreceptors to stimulate AVP release while activating the NTS, AP, and LPBN in addition to the SON and PVN.
Hypertension is a major health problem that significantly contributes to heart disease and stroke... more Hypertension is a major health problem that significantly contributes to heart disease and stroke. While most studies of hypertension have focused on men, women also experience significant hypertension-related morbidity and mortality. However, the incidence of hypertension and cardiovascular disease is significantly lower in premenopausal women compared with men until the onset of menopause, at which time cardiovascular disease incidence increases dramatically in women and eventually approaches that in men. These observations indicate that the loss of estrogen contributes to menopause-related increases in blood pressure and cardiovascular disease, and suggest that the use of estrogen hormone replacement therapy could decrease the incidence of cardiovascular disease in postmenopausal women. However, new findings from the Women's Health Initiative study suggest that estrogen therapy has few positive benefits and some significant negative effects on the health of postmenopausal women, and these data have caused many to abandon long-term estrogen replacement therapy. Conversely, numerous clinical and basic research studies indicate that estrogen replacement therapy beneficially reduces blood pressure, thereby decreasing the incidence of hypertension and cardiovascular disease. Further, several of these studies suggest that one means by which estrogen lowers blood pressure is by decreasing sympathetic nervous system activity. This review examines the evidence supporting estrogen's ability to modulate sympathetic nervous system tone and thereby decrease arterial pressure.
International Journal of Sport Psychology, Sep 1, 2012
ABSTRACT The Contextual Sensation Seeking Questionnaire (CSSQ-S) was developed to measure pattern... more ABSTRACT The Contextual Sensation Seeking Questionnaire (CSSQ-S) was developed to measure patterns of sensation-seeking behaviours in skiing and snowboarding. We conducted three studies supporting several aspects of its validity. First, using a focus group (n = 4) we generated items representative of sensation seeking in skiing and explored the factor structure in a sample of skiers (n1 = 220). Second, we confirmed the factor structure using data from an independent cohort (n2 = 530). Finally, we provide evidence for criterion-relevance and applied utility of CSSQ-S scores by demonstrating positive relationships between scores and self-reported injury. CSSQ-S scores explained greater variance (n1 = 217, β = .358, p < .001) in injury prevalence than an established assessment tool (Zuckerman’s Impulsive-Sensation Seeking scale). In summary, the CSSQ-S represents a psychometrically promising measure of contextual sensation seeking and may be used to explore factors associated with risk-taking in skiing and snowboarding.
Several lines of evidence suggest that peripheral osmoreceptors respond to alterations in dietary... more Several lines of evidence suggest that peripheral osmoreceptors respond to alterations in dietary NaCl by adjusting renal sympathetic nerve activity, but the impact of this reflex on the long-term regulation of mean arterial pressure (MAP) remains unclear. The present study tested the hypothesis that denervation of peripheral osmoreceptors elevates arterial pressure and induces NaCl-sensitive hypertension in normotensive rats. Hepatic denervated
P300 amplitude predicts substance use or disorder by age 21. Earlier- versus later-onset substanc... more P300 amplitude predicts substance use or disorder by age 21. Earlier- versus later-onset substance disorders may reflect different levels of an externalizing psychopathology dimension. P300 in adolescence may not be as strongly related to later-onset substance problems as it is to earlier-onset ones. In the present study, visual P300 amplitude was measured at age 17 in a community-representative sample of young men. Substance and externalizing disorders were assessed at approximately ages 17, 20, and 24. Earlier-onset (by age 20) substance disorder was associated with higher rates of externalizing disorders than were later-onset problems. P300 amplitude was reduced in subjects with earlier-onset substance disorders, relative to later-onset and disorder-free subjects. Amplitude was also reduced in subjects with an externalizing disorder but no substance disorder. Earlier-onset subjects had reduced P300, even in the absence of an externalizing disorder. The results could not be attributed to a concurrent disorder or to recent substance use at the time of the P300 recording. The findings are consistent with P300 indexing an externalizing spectrum. Earlier-onset substance disorders are more strongly related to P300 and externalizing than are later-onset problems.
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