Oxytocin augments baroreflex bradycardia in conscious rats

Russ, R. D.; Walker, Benjimen R.

doi:10.1016/0196-9781(94)90049-3

Cited by 19 publications

(23 citation statements)

References 26 publications

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“…The reduction in heart rate is consistent with the baroreflex responses seen with other a 1 agonists such as methoxamine and midodrine [12,26]. Although it is not clear what all of the modifiers are of this reflex [27][28][29][30], the role of the a 1 -adrenoceptor evoking a response is supported by the reduction in heart rate caused by agonists and the increase in heart rate by antagonists such as prazosin [31,32].…”

Section: Discussionsupporting

confidence: 57%

A randomized crossover study to evaluate Ro 115–1240, a selective α_1A/1L‐adrenoceptor partial agonist in women with stress urinary incontinence

et al. 2003

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RESULTSRo 115-1240 was associated with a significantly lower mean weekly number of SUI episodes than placebo (8.4 vs 6.0; P = 0.0079), a 28% relative improvement over placebo. There was also a significantly lower mean number of pads used and wet pads changed/week with Ro 115-1240 than with placebo ( P = 0.0055 and 0.0066, respectively). The most frequently reported treatmentemergent adverse events were scalp tingling, headache, chills, piloerection, and pruritus. Generally these events were transient and mild to moderate. There was a slightly lower mean sitting heart rate with Ro 115-1240 than with placebo, but no difference in mean systolic or diastolic blood pressure between treatments. CONCLUSIONSThis study suggests that selective a 1A/1 Ladrenoceptor partial agonists have the potential to improve the symptoms of SUI with little or no cardiovascular effect. These results are encouraging and a randomized controlled trial of Ro 115-1240 in a larger population with SUI is warranted to substantiate these findings. KEYWORDSstress urinary incontinence, a -adrenoceptor, blood pressure OBJECTIVESTo investigate the potential therapeutic benefits of the selective a 1A/1 L -adrenoceptor partial agonist Ro 115-1240 in women with mild-to-moderate stress urinary incontinence (SUI). PATIENTS AND METHODSThirty-seven women with mild-to-moderate SUI were enrolled in a randomized, placebocontrolled crossover study. Patients received 1.5 mg Ro 115-1240 twice daily or matching placebo for 2 or 4 weeks. Voiding diaries were used to record the number of SUI episodes, urge incontinence episodes and pads used. Sitting blood pressures and heart rate were recorded at each visit.

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Section: Discussionsupporting

confidence: 57%

A randomized crossover study to evaluate Ro 115–1240, a selective α_1A/1L‐adrenoceptor partial agonist in women with stress urinary incontinence

et al. 2003

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“…Previous data from our and other laboratories indicated an important role of OT within the dorsal brain stem and the involvement of PVN OTergic projections in the modulation of HR control. Oxytocin acted in the NTS/dorsal motor nucleus of the vagus (DMV) complex to facilitate vagal outflow and reflex bradycardia during baroreceptor loading in normotensive rats (11,16,39). Oxytocin receptor blockade in the NTS reduced reflex bradycardia (16) and increased the tachycardic response to an acute bout of exercise (6,25,27).…”

Section: Discussionmentioning

confidence: 99%

“…The effects of training on HR responses were attributable to activation of OTergic pathways from the hypothalamus to dorsal brain stem (6,17,23,25,27), and OT has been shown to be involved in the baroreceptor reflex control of HR (11,16,37,39,43) and heart protection (14,19,21). We hypothesized that sinoaortic denervation (SAD) would affect the central OTergic drive that modulates the autonomic control of the heart in normotensive and hypertensive rats.…”

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confidence: 99%

Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity

Cavalleri

Burgi

Cruz

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Michelini LC. Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity. Am J Physiol Regul Integr Comp Physiol 301: R958 -R966, 2011. First published July 27, 2011 doi:10.1152/ajpregu.00104.2011.-We showed previously that oxytocinergic (OTergic) projections from the hypothalamic paraventricular nucleus (PVN) to the dorsal brain stem mediate traininginduced heart rate (HR) adjustments and that beneficial effects of training are blocked by sinoaortic denervation (SAD; Exp Physiol 94: 630 -640; 1103-1113). We sought now to determine the combined effect of training and SAD on PVN OTergic neurons in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats underwent SAD or sham surgery and were trained (55% of maximal capacity) or kept sedentary for 3 mo. After hemodynamic measurements were taken at rest, rats were deeply anesthetized. Fresh brains were frozen and sliced to isolate the PVN; samples were processed for OT expression (real-time PCR) and fixed brains were processed for OT immunofluorescence. In sham rats, training improved treadmill performance and increased the gain of baroreflex control of HR. Training reduced resting HR (Ϫ8%) in both groups, with a fall in blood pressure (Ϫ10%) only in SHR rats. These changes were accompanied by marked increases in PVN OT mRNA expression (3.9-and 2.2-fold in WKY and SHR rats, respectively) and peptide density in PVN OTergic neurons (2.6-fold in both groups), with significant correlations between OT content and training-induced resting bradycardia. SAD abolished PVN OT mRNA expression and markedly reduced PVN OT density in WKY and SHR. Training had no effect on HR, PVN OT mRNA, or OT content following SAD. The chronic absence of inputs from baroreceptors and chemoreceptors uncovers the pivotal role of afferent signaling in driving both the plasticity and activity of PVN OTergic neurons, as well as the beneficial effects of training on cardiovascular control. sinoaortic denervation; exercise training; hypothalamus; paraventricular nucleus; supraoptic nucleus; oxytocin; spontaneous hypertension ACCUMULATING EXPERIMENTAL evidence from our and other laboratories has shown that aerobic training promotes several beneficial cardiovascular effects in normotensive and hypertensive individuals. Training causes remodeling of the heart with a simultaneous stroke volume increase and heart rate (HR) decrease (5, 34, 40), outward eutrophic remodeling of arterioles, capillary angiogenesis, and venule neoformation in the exercised muscles (1-3, 10, 24). Exercise training is also accompanied by a predominance of relaxation over contractile endothelium-derived factors (15, 44). These adaptive mechanisms by improving blood flow and tissue conductance, by reducing vascular resistance, and restoring normal endothelial function favor the amelioration of impaired functions in cardiovascular disease.Training reduces both the activity of the renin-angiotensin system and oxidative stress (13,22,38) and effectively induces neuronal pla...

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“…[27][28][29] Brainstem administrations of OT or OT receptor antagonist did change local neuronal activity 18 -19 and the autonomic control of the heart. 15,20 Functional experiments in conscious, normotensive rats showed that NTS oxytocinergic projections exert a tonic effect on HR control, facilitating vagal outflow and reflex bradycardia during baroreceptors loading. 15 We also demonstrated in normotensive, trained rats running on a treadmill that the increased OT release within the DBS was the main determinant of the reduced tachycardic response observed after training.…”

Section: Discussionmentioning

confidence: 99%

Hypertension and Exercise Training Differentially Affect Oxytocin and Oxytocin Receptor Expression in the Brain

et al. 2005

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Abstract-We have previously shown that exercise training activates nucleus tractus solitarii (NTS) oxytocinergic projections, resulting in blunted exercise tachycardia. The objective of this study was to determine the effects of hypertension and training on oxytocin (OT) and OT receptor expression in the hypothalamic paraventricular nucleus (PVN) and projection areas (dorsal brain stem [DBS]). Male, normotensive, Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were trained (55% maximal exercise capacity, 3 months) or kept sedentary, and pressure was measured weekly. DBS sections were processed for immunohistochemistry (polyclonal guinea pig anti-OT) or in situ hybridization for OT and OT receptor ( 35 S-oligonucleotide probes). Other groups of rats had brains removed and frozen to isolate the DBS and PVN; samples were processed for OT and OT receptor cDNA reverse transcription-polymerase chain reaction amplification with ␤-actin as the housekeeping gene. Training was equally effective in improving running distance in both groups, with pressure reduction only in SHR (Ϫ10%, PϽ0.05). In trained WKY, baseline bradycardia (PϽ0.05) occurred simultaneously with increased NTS OT immunostaining and mRNA expression (ϩ3.5-fold), without any change in OT receptor mRNA expression. PVN OT mRNA and DBS OT receptor mRNA expressions were significantly lower in SHR versus WKY (Ϫ39% and Ϫ56%, respectively). Training did not alter DBS OT receptor density in the SHR group but increased OT mRNA in both PVN and DBS areas (ϩ78% and ϩ45%, respectively). Our results show a marked hypertension-induced reduction in OT receptor mRNA expression, not altered by training. In contrast, training increased OT mRNA expression in sedentary and hypertensive rats, which may facilitate traininginduced cardiac performance. Key Words: hypothalamus Ⅲ exercise Ⅲ rats, spontaneously hypertensive Ⅲ neurotransmitter Ⅲ genetics Ⅲ autonomic nervous system Ⅲ immunohistochemistry H ypertension is a highly prevalent disease and a common risk factor for different cardiovascular diseases, with a major impact on morbidity and mortality. 1 Hypertensive individuals present with a series of functional and anatomic deficits, such as increased vascular resistance, vessel rarefaction, increased heart energy expenditure, increased stroke work, impaired baroreceptor reflex control, hormonal imbalance with overactivation of the renin-angiotensin system, and increased insulin resistance. Most of these effects contribute to increased sympathetic activity and depressed cardiovascular control. 1 On the other hand, exercise training has been associated with a variety of beneficial cardiovascular adjustments in hypertensive individuals, such as eutrophic remodeling of arterioles causing wall-lumen ratio normalization, 2,3 capillary angiogenesis and venule neoformation in exercised muscles resulting in increased vascular capacity and O 2 extraction, 3-7 and remodeling of the heart with simultaneous stroke volume increase and heart rate decrease. 8,9 Although there are ...

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Oxytocin augments baroreflex bradycardia in conscious rats

Cited by 19 publications

References 26 publications

A randomized crossover study to evaluate Ro 115–1240, a selective α_1A/1L‐adrenoceptor partial agonist in women with stress urinary incontinence

A randomized crossover study to evaluate Ro 115–1240, a selective α_1A/1L‐adrenoceptor partial agonist in women with stress urinary incontinence

Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity

Hypertension and Exercise Training Differentially Affect Oxytocin and Oxytocin Receptor Expression in the Brain

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Oxytocin augments baroreflex bradycardia in conscious rats

Cited by 19 publications

References 26 publications

A randomized crossover study to evaluate Ro 115–1240, a selective α1A/1L‐adrenoceptor partial agonist in women with stress urinary incontinence

A randomized crossover study to evaluate Ro 115–1240, a selective α1A/1L‐adrenoceptor partial agonist in women with stress urinary incontinence

Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity

Hypertension and Exercise Training Differentially Affect Oxytocin and Oxytocin Receptor Expression in the Brain

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A randomized crossover study to evaluate Ro 115–1240, a selective α_1A/1L‐adrenoceptor partial agonist in women with stress urinary incontinence

A randomized crossover study to evaluate Ro 115–1240, a selective α_1A/1L‐adrenoceptor partial agonist in women with stress urinary incontinence