Sympathoinhibitory effects of rilmenidine may be mediated by sites located below the brainstem

Sannajust, Frederick; Barrès, Christian; Koenig-Berard, Elisabeth; Sassard, J

doi:10.1111/j.1476-5381.1992.tb09015.x

Cited by 18 publications

(5 citation statements)

References 24 publications

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“…Interestingly, integrated nerve activity appeared less sensitive to the compound in that the proportional decreases in nerve activity were only about half those in blood pressure; this is a general indicator of sympathetic outflow, in both normotensive and hypertensive animals. Nevertheless, the renal sympatho-inhibition observed at this dose was comparable to that obtained by others in anaesthetized and conscious normotensive and hypertensive rats (Sannajust et al, 1992;Kline & Cechetto, 1993) and rabbits (Szabo et al, 1993) and has been considered by some to be due to activation of imidazoline receptors by rilmenidine in the rostral venterolateral medulla of the brain. However, this remains a contentious area as two recent studies by Uban et al (1995a, b) in the rabbit, have been unable convincingly to distinguish pharmacologically between the cardiovascular effects of a highly selective CX2-adrenoceptor agonist (ie UK14304) and monoxidine and rilmenidine.…”

Section: Discussionsupporting

confidence: 89%

“…Administration of rilmenidine systemically led to dose-dependent reductions in blood pressure and heart rate in both Wistar and SHRSP that were comparable to those obtained previously in these rat strains, albeit at slightly different doses and modes of administration, eg, continuous infusion versus bolus doses (Sannajust et al, 1992;Kline & Cechetto, 1993). Interestingly, integrated nerve activity appeared less sensitive to the compound in that the proportional decreases in nerve activity were only about half those in blood pressure; this is a general indicator of sympathetic outflow, in both normotensive and hypertensive animals.…”

Section: Discussionsupporting

confidence: 79%

“…A number of studies in the rat (Sannajust et al, 1992; Kline & Cechetto, 1993) and rabbit (Szabo et al, 1993;Head et al, 1993) showed that both central and peripheral administration of rilmenidine causes an inhibition Brftish Journal of Pharmacology (1996) 119,[1248][1249][1250][1251][1252][1253][1254] T. Zhang & E.J. Johns Rilmenidine and renal nerve activy of sympathetic nerve activity to the kidney.…”

Section: Introductionmentioning

confidence: 99%

“…There is evidence showing that rilmenidine acts at imidazoline receptors, which are present within the rostral venterolateral medulla (Ernzberger et al, 1990), to cause a decrease in sympathethic outflow with a subsequent decrease in total peripheral resistance and heart rate which contributes to the fall in blood pressure. A number of studies in the rat (Sannajust et al, 1992; Kline & Cechetto, 1993) and rabbit (Szabo et al, 1993;Head et al, 1993) showed that both central and peripheral administration of rilmenidine causes an inhibition Brftish Journal of Pharmacology (1996) 119,[1248][1249][1250][1251][1252][1253][1254] of sympathetic nerve activity to the kidney. This renal sympatho-inhibition was more apparent in spontaneously hypertensive rats (SHR) and the magnitude of the inhibition was dose-dependent.…”

Section: Introductionmentioning

confidence: 99%

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Rilmenidine and reflex renal sympathetic nerve activation in wistar and hypertensive rats

Zhang¹,

Johns²

1996

British J Pharmacology

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1 This study sets out to examine the effect of rilmenidine administered systemically on basal and reflexly activated renal nerve activity in Wistar and stroke prone spontaneously hypertensive rats (SHRSP). 2 Animals were anaesthetized with chloralose/urethane, stimulating electrodes were placed on the brachial plexi and the renal nerves were isolated and put on recording electrodes. Both brachial nerves were stimulated electrically at 0.8, 1.6 and 3.2 Hz (15 V, 0.2 ms) in the absence and in the presence of rilmenidine given at 100 and 200 y'g kg-' i.v. in a cumulative manner. 3 Stimulation of the brachial nerves caused graded increases in blood pressure, heart rate and integrated renal nerve activity (P<0.05) in both Wistar and SHRSP. Fast Fourier transformation of the renal nerve activity signal to generate a power spectrum demonstrated that both total power and percentage power at heart rate was higher in the SHRSP than Wistar (P<0.05). Total power was raised during brachial nerve stimulation in both Wistar and SHRSP by some 200-300% (P<0.05) but the percentage power at heart rate was decreased by some 60% (P<0.01) in the Wistar but was raised by some 40-50% (P<0.05) in the SHRSP. 4 Administration of rilmenidine caused dose-related decreases in blood pressure and heart rate and integrated renal nerve activity in both Wistar and SHRSP (all P<0.05). Both doses of rilmenidine decreased (P<0.05) the total power in the signal in both strains of rat by about one-half but the power occurring at heart rate only fell at the higher dose of compound in the Wistar, whereas in the SHRSP it was decreased by both doses by approximately 60-70%. In the presence of rilmenidine, coherence of the renal nerve signal was reduced in the Wistar and SHRSP and although the drug had no effect on phase difference in the Wistar, this parameter was decreased in the SHRSP by the low and high doses of rilmenidine (P <0.05). 5 In the presence of 100 pig kg-' rilmenidine, stimulation of the brachial nerves caused increases in total power in the Wistar and SHRSP (two to three fold, P< 0.05), together with a decrease (P <0.05) in the percentage power occuring at heart rate in the Wistar, of some 60%, and an increase (P < 0.01) in the SHRSP, of some two to three times, which were very similar in magnitude and pattern to those obtained in the absence of the drug. Following the 200 pig kg'-dose of rilmenidine, brachial nerve stimulation increased total power in the Wistar and SHRSP groups (P <0.05) and whereas in the Wistar the percentage power at heart rate did not change in the SHRSP it was again increased in response to the electrical stimulation of the brachial plexus (P<0.001) by between two to three fold. 6 These results showed that in both the Wistar and SHRSP rilmenidine depressed blood pressure, heart rate and integrated renal nerve activity. Moreover, rilmenidine did not affect the reflex activation of renal nerve activity via the somatosensory system although the characteristics within the power spectra underwent certain changes which mi...

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rilmenidine and reflex renal sympathetic nerve activation in wistar and hypertensive rats

Zhang¹,

Johns²

1996

British J Pharmacology

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“…The reason of this discrepancy is not readily apparent. The extent of drugs-induced antihypertensive effect has been reported to closely depend upon the level of blood pressure [40,41]. Thus, it is not unlikely to postulate that differences in sildenafil citrate effect observed in our study might be due to the level of blood pressure and/or the pre-existing level of cardiovascular alterations ( i .…”

Section: Discussionmentioning

confidence: 57%

Sildenafil citrate long-term treatment effects on cardiovascular reactivity in a SHR experimental model of metabolic syndrome

Doghri¹,

Chetaneau²,

Rhimi³

et al. 2019

PLoS ONE

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Much evidence indicates that metabolic syndrome is strongly correlated with a decrease in nitric oxide and an increase in oxidative stress leading to cardiovascular alterations. In recent years, gut microbiota has emerged as a new contributor to the metabolic syndrome establishment and associated cardiovascular diseases, but the underlying mechanisms remain unclear. We hypothesized that a positive modulation of cyclic guanosine monophosphate (cGMP) pathway, through phosphodiesterase type 5 (PDE5) inhibition could prevent cardiovascular alterations and gut dysbiosis that may be associated to metabolic syndrome. Spontaneously hypertensive rats (SHR) were randomly divided into 4 groups: control, cafeteria diet (CD) and sildenafil citrate treated groups (5mg/kg per os) were given either a CD or a standard chow diet for 10 weeks. Body weight, arterial blood pressure and glucose tolerance test were monitored. At the 10th week, cardiac inotropy and coronary perfusion pressure were evaluated on isolated heart according to Langendorff method. Cumulative concentration response curves to phenylephrine and acetylcholine were determined on thoracic aorta rings for vascular reactivity evaluation. Faecal samples were collected for the gut microbiota analysis. Compared to the control group, CD-fed rats showed a significant increase in body weight gain, arterial blood pressure and were glucose intolerant. This group showed also a decrease in β-adrenoceptor-induced cardiac inotropy and coronary vasodilation. Gut microbiota analysis revealed a significant reduction in the abundance of Lactobocillus spp in cafeteria diet-fed rats when compared to the control ones. Sildenafil citrate long-term treatment decreased weight gain and arterial blood pressure, improved coronary vasodilation and reduced α1-adrenoceptor-induced vasoconstriction in CD group. However, it did not reverse gut dysbiosis induced by chronic CD feeding. These results suggest that cGMP pathway targeting may be a potential therapeutic strategy for the management of the metabolic syndrome and associated cardiovascular disorders.

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Sympathoinhibition by rilmenidine in conscious rabbits: involvement of ?2-adrenoceptors

Szabó

Urban

Starke

1993

Naunyn-Schmiedeberg's Arch Pharmacol

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Cardiovascular and sympathetic nervous system effects of the mixed alpha 2-adrenoceptor and imidazoline receptor agonist rilmenidine were studied in conscious rabbits chronically instrumented for the recording of the firing rate of renal sympathetic fibers. Separate experiments were carried out on pithed rabbits with electrically stimulated (2 Hz) sympathetic outflow. Drugs were administered intravenously in a cumulative manner. In conscious rabbits, rilmenidine 0.1, 0.3 and 1.0 mg kg-1 dose-dependently lowered blood pressure, renal sympathetic nerve activity, heart rate and the plasma concentration of noradrenaline and adrenaline. The effect on blood pressure and plasma catecholamines was maximal after 0.3 mg kg-1 whereas heart rate and renal sympathetic nerve activity decreased further after rilmenidine 1.0 mg kg-1. Yohimbine 0.1 and 0.5 mg kg-1, when injected subsequently, attenuated and at the higher dose abolished all effects of rilmenidine. The effects of rilmenidine were also antagonized by the alpha 2-adrenoceptor antagonist 2-(2,3-dihydro-2-methoxy-1,4-benzodioxin-2-yl)-4,5-dihydro-1H-imid azole HCl (RX821002; 0.1 and 0.5 mg kg-1). Yohimbine 0.1 and 0.5 mg kg-1 did not attenuate or attenuated only slightly the decrease of heart rate and renal sympathetic nerve activity produced by infusion of vasopressin. In pithed rabbits with electrically-stimulated sympathetic outflow, yohimbine 0.1 submaximally and yohimbine 0.5 mg kg-1 maximally increased the plasma noradrenaline concentration. The experiments show by direct measurement of sympathetic nerve firing and plasma catecholamines that rilmenidine causes sympathoinhibition in conscious rabbits, presumably through central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)

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Sympathoinhibitory effects of rilmenidine may be mediated by sites located below the brainstem

Cited by 18 publications

References 24 publications

Rilmenidine and reflex renal sympathetic nerve activation in wistar and hypertensive rats

Rilmenidine and reflex renal sympathetic nerve activation in wistar and hypertensive rats

Sildenafil citrate long-term treatment effects on cardiovascular reactivity in a SHR experimental model of metabolic syndrome

Sympathoinhibition by rilmenidine in conscious rabbits: involvement of ?2-adrenoceptors

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