Actions of rilmenidine on neurogenic hypertension in BPH/2J genetically hypertensive mice

Jackson, Kristy L.; Palma‐Rigo, Kesia; Nguyen‐Huu, Thu‐Phuc; Davern, Pamela J.; Head, Geoffrey A.

doi:10.1097/hjh.0000000000000036

Cited by 6 publications

(11 citation statements)

References 61 publications

(80 reference statements)

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“…Thus our study is novel for this type of analysis in SHR. We have previously reported that the rate of rise in MAP in hypertensive BPH/2J mice and normotensive control strain BPN/3J was largely attenuated by administration of rilmenidine via minipump [20]. The extent of the BP lowering by rilmenidine was also similar to the present study but we did not report on whether the effect was observed in SAP or DAP [20].…”

Section: Discussionsupporting

confidence: 80%

“…The anti-hypertensive agents used were perindopril (1mg/kg/day), or rilmenidine (2mg/kg/day), which we have shown to have antihypertensive properties [20, 23–25]. We determined the concentration by measuring the water intake of the rats for at least 48 hours and adjusting individual water intake and body weight of the rats on a weekly basis.…”

Section: Methodsmentioning

confidence: 99%

“…Rilmenidine is also known to facilitate the cardiac baroreflex through greater vagal activity but only during the light inactive period in mice [20]. We have also observed that rilmenidine reduced the rate of rise in BP that occurs at the onset of darkness in hypertensive mice [20]. However, we do not know the effect of rilmenidine on the arousal BP Power nor whether this is simply due to a reduction in BP itself.…”

Section: Introductionmentioning

confidence: 97%

“…The principle antihypertensive effects of rilmenidine and moxonidine are through inhibition of sympathetic activity [16] and this involves mainly activation of imidazoline receptors in the rostral ventrolateral medulla [17–19]. Rilmenidine is also known to facilitate the cardiac baroreflex through greater vagal activity but only during the light inactive period in mice [20]. We have also observed that rilmenidine reduced the rate of rise in BP that occurs at the onset of darkness in hypertensive mice [20].…”

Section: Introductionmentioning

confidence: 98%

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The Effects of Rilmenidine and Perindopril on Arousal Blood Pressure during 24 Hour Recordings in SHR

et al. 2016

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The surge in arterial pressure during arousal in the waking period is thought to be largely due to activation of the sympathetic nervous system. In this study we compared in SHR the effects of chronic administration of the centrally acting sympatholytic agent rilmenidine with an angiotensin converting enzyme inhibitor perindopril on the rate of rise and power of the surge in mean arterial pressure (MAP) that occurs with arousal associated with the onset of night. Recordings were made using radiotelemetry in 17 adult SHR before and after treatment with rilmenidine (2mg/kg/day), perindopril (1mg/kg/day) or vehicle in the drinking water for 2 weeks. Rilmenidine reduced MAP by 7.2 ± 1.7mmHg while perindopril reduced MAP by 19 ± 3mmHg. Double logistic curve fit analysis showed that the rate and power of increase in systolic pressure during the transition from light to dark was reduced by 50% and 65%, respectively, but had no effect on diastolic pressure. Rilmenidine also reduced blood pressure variability in the autonomic frequency in the active period as assessed by spectral analysis which is consistent with reduction in sympathetic nervous system activity. Perindopril had no effect on the rate or power of the arousal surge in either systolic or diastolic pressure. These results suggest that the arousal induced surge in blood pressure can largely be reduced by an antihypertensive agent that inhibits the sympathetic nervous system and that angiotensin converting enzyme inhibition, while effective in reducing blood pressure, does not alter the rate or power of the surge associated with arousal.

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Section: Discussionsupporting

confidence: 80%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

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The Effects of Rilmenidine and Perindopril on Arousal Blood Pressure during 24 Hour Recordings in SHR

et al. 2016

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“…24 Furthermore, the rapid and pronounced bradycardic effects of intraperitoneal almorexant in BPH/2J mice are similar to the acute effects observed after intraperitoneal administration of rilmenidine, another centrally acting sympatholytic agent, which was shown to produce hypotensive effects in BPH/2J mice predominantly via a vagal excitatory effect rather than its sympatholytic effect. 25 Indeed, orexin is capable of increasing HR by indirect vagal inhibition. 26 However, it is unclear from the present findings, how much of the bradycardic effect of almorexant in BPH/2J mice is because of a decrease in SNS activity compared with an increase in vagal activity.…”

Section: Effect Of Almorexant On Hrmentioning

confidence: 99%

Contribution of Orexin to the Neurogenic Hypertension in BPH/2J Mice

et al. 2016

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BPH/2J mice are a genetic model of hypertension which were selectively bred for elevated blood pressure (BP) in the 1970s alongside a normotensive strain (BPN/3J).1 Recent studies suggest that the hypertension in BPH/2J mice is caused by enhanced activation of the sympathetic nervous system (SNS) because ganglion blockade causes a greater depressor response in BPH/2J mice compared with BPN/3J controls. 2,3 Importantly, cardiovascular regulatory forebrain regions within the hypothalamus and amygdala display markedly greater neuronal activity in BPH/2J compared with BPN/3J mice during the dark-active period of the 24-hour light cycle.2 Furthermore, lesions of the medial amygdala reduced the hypertension and SNS overactivity in BPH/2J mice. 4 Thus the central nervous system seems to play a crucial role in driving the sympathetically mediated hypertension in this model.A gene array approach has been used to identify differential expression of genes in the hypothalamus between BPH/2J and BPN/3J mice. 5,6 An important finding was that expression of the orexin precursor gene (hcrt) in BPH/2J mice was more than double that of normotensive mice in early and established hypertension. Thus, hcrt could potentially contribute to the development and maintenance of BPH/2J hypertension.5 Furthermore, BPH/2J mice have ≈4-fold greater expression of the hcrt gene in the hypothalamus during the dark-active period compared with light period when mice are predominantly inactive or asleep. 6 Characteristics of the BPH/2J mouse strain, such as high BP, tachycardia, greater locomotor activity, overactivity of the SNS, 2 and exaggerated cardiovascular reactivity to stressful stimuli, 7 could all be reflective of a greater activity of the orexinergic neurons. Indeed, orexin is capable of increasing BP, heart rate (HR), and SNS activity.8 Orexinergic neurons originate in the hypothalamus and project to a wide range of brain regions, but in terms of sympathetic control of BP, the Abstract-BPH/2J mice are a genetic model of hypertension associated with an overactive sympathetic nervous system.Orexin is a neuropeptide which influences sympathetic activity and blood pressure. Orexin precursor mRNA expression is greater in hypothalamic tissue of BPH/2J compared with normotensive BPN/3J mice. To determine whether enhanced orexinergic signaling contributes to the hypertension, BPH/2J and BPN/3J mice were preimplanted with radiotelemetry probes to compare blood pressure 1 hour before and 5 hours after administration of almorexant, an orexin receptor antagonist. Mid frequency mean arterial pressure power and the depressor response to ganglion blockade were also used as indicators of sympathetic nervous system activity. Administration of almorexant at 100 (IP) and 300 mg/ kg (oral) in BPH/2J mice during the dark-active period (2 hours after lights off) markedly reduced blood pressure (−16.1±1.6 and −11.0±1.1 mm Hg, respectively; P<0.001 compared with vehicle). However, when almorexant (100 mg/ kg, IP) was administered during the light-inactive pe...

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Identification and Application of Gene Expression Signatures Associated with Lifespan Extension

et al. 2019

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Actions of rilmenidine on neurogenic hypertension in BPH/2J genetically hypertensive mice

Cited by 6 publications

References 61 publications

The Effects of Rilmenidine and Perindopril on Arousal Blood Pressure during 24 Hour Recordings in SHR

The Effects of Rilmenidine and Perindopril on Arousal Blood Pressure during 24 Hour Recordings in SHR

Contribution of Orexin to the Neurogenic Hypertension in BPH/2J Mice

Identification and Application of Gene Expression Signatures Associated with Lifespan Extension

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