Clonidine Reduces Blood Pressure and Heart Rate Oscillations in the Conscious Rat

Grichois, Marie‐Laure; Japundžić, Nina; Head, Geoffrey A.; Elghozi, Jean‐Luc

doi:10.1097/00005344-199009000-00015

Cited by 34 publications

(23 citation statements)

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“…The present study showed that clonidine elicited hypotension in control SHRs and significantly reduced time-domain indices of blood pressure and heart rate variability (SDMAP, SDRR, and rMSSD). These findings are in agreement with previous reports that used time-or frequency-domain measurements and highlight a role for the concomitant reduction in central sympathetic outflow in mediating clonidine effects (Grichois et al, 1990;Elghozi et al, 1991;Janssen et al, 1991;Tulen et al, 1993). The brief pressor effect that preceded clonidine hypotension might be related to the stress associated with the intraperitoneal injection of the drug because a similar response followed saline administration.…”

Section: Discussionsupporting

confidence: 93%

“…Ethanol also attenuated the parallel reductions in blood pressure and heart rate variability elicited by clonidine. Given the positive correlation between clonidine-evoked reduction in hemodynamic variability and sympathoinhibition (Grichois et al, 1990;Elghozi et al, 1991;Janssen et al, 1991;Tulen et al, 1993) and the importance of sympathoexcitation in the ethanol counteraction of centrally evoked hypotension (El-Mas et al, 1994b;Mao and Abdel-Rahman, 1998), the attenuation by ethanol of clonidine effects on blood pressure and heart rate variability supports the involvement of the sympathetic component in the interaction. Together, these findings demonstrate that chronic ethanol administration compromises clonidine-induced hemodynamic stability and sympathoinhibition, which may contribute to the antagonistic effect of the two drugs on blood pressure.…”

Section: Discussionmentioning

confidence: 98%

“…Time-domain indices correlate with frequency-domain measurements and, therefore, provide a reliable evaluation of cardiovascular autonomic balance (Stein et al, 1994;Sgoifo et al, 1997). The results showed that clonidine produced hypotension that was associated with significant reductions in the time-domain indices of MAP (SDMAP) and heart rate (SDRR and rMSSD) variability, which may reflect the clonidine-evoked inhibition of central sympathetic activity (Grichois et al, 1990;Elghozi et al, 1991;Janssen et al, 1991;Tulen et al, 1993). Ethanol feeding, concentration dependently, attenuated the hypotensive effect of clonidine and the associated reductions in MAP and heart rate variability.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to sympathoinhibition, two others factors have been proposed to contribute to the hemodynamic stability produced by clonidine. First, Grichois et al (1990) and Elghozi et al (1991) suggested that the increased arterial baroreflex responsiveness by clonidine might contribute to the better control of blood pressure and heart rate oscillations. Notably, baroreflex activity is inversely related to blood pressure variability (Su et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…Sympathoinhibition has also been implicated in the clonidine-induced reductions in blood pressure and heart rate variability as determined by frequency-and time-domain analyses (Grichois et al, 1990;Elghozi et al, 1991;Janssen et al, 1991;Tulen et al, 1993). The reduction in hemodynamic variability by clonidine is important at least in two clinical settings.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Chronic Ethanol Feeding on Clonidine-Evoked Reductions in Blood Pressure, Heart Rate, and Their Variability: Time-Domain Analyses

El‐Mas

Abdel‐Rahman²

2003

J Pharmacol Exp Ther

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The effects of chronic ethanol administration on the acute hemodynamic effects of clonidine were investigated in conscious radiotelemetered spontaneously hypertensive rats (SHRs). Changes evoked by clonidine (30 g/kg i.p.) in blood pressure, heart rate, and their variability were evaluated in ethanol [2.5 or 5% (w/v), 12 weeks] and pair-fed control rats. The blood pressure variability was determined as the standard deviation of the mean arterial pressure (SDMAP). Two heart rate variability indices were used, the standard deviation of beat-tobeat intervals (SDRR) and the root mean square of successive beat-to-beat differences in R-R interval durations (rMSSD). Compared with control rats, ethanol (2.5 and 5%)-fed rats exhibited concentration-related reductions in mean arterial pressure (MAP) and SDMAP versus no change in heart rate variability. In control rats, clonidine caused a significant reduction in MAP that continued for at least 5 h and was associated with significant reductions in SDMAP, SDRR, and rMSSD, responses that are consistent with the inhibition of central sympathetic tone. The hypotensive effect of clonidine was attenuated by ethanol in a concentration-related manner. The maximum reductions in MAP elicited by clonidine in ethanol (2.5 and 5%)-fed rats amounted to Ϫ23.4 Ϯ 2.8 and Ϫ15.1 Ϯ 1.5 mm Hg, respectively, compared with Ϫ35.4 Ϯ 1.2 mm Hg in control rats. The clonidine-induced reductions in SDMAP, SDRR, and rMSSD were also significantly attenuated by ethanol. These findings suggest that the attenuation of MAP and heart rate variability responses elicited by clonidine in ethanolfed SHRs reflects alterations in the sympathovagal balance, which may be implicated in the antagonistic hemodynamic interaction between the two drugs.Clonidine is a centrally acting antihypertensive drug that decreases blood pressure predominantly via stimulation of ␣ 2 -adrenergic (Timmermans and van Zwieten, 1982) and imidazoline (Tibirica et al., 1991) receptors in the brainstem, resulting in suppression of central sympathetic outflow. Sympathoinhibition has also been implicated in the clonidine-induced reductions in blood pressure and heart rate variability as determined by frequency-and time-domain analyses (Grichois et al., 1990;Elghozi et al., 1991;Janssen et al., 1991;Tulen et al., 1993). The reduction in hemodynamic variability by clonidine is important at least in two clinical settings. First, the long-term reduction in blood pressure variability by clonidine may contribute to the regression of ventricular and vascular hypertrophy in hypertensive patients (Timio et al., 1987;Strauer, 1988). Second, by reducing blood pressure and heart rate variability, clonidine promotes hemodynamic stability in patients undergoing surgery and reduces anesthetic requirements (Nishikawa et al., 1991). It is noteworthy that 1) blood pressure and heart rate variability is an indirect measure of cardiovascular autonomic balance and 2) oscillation abnormalities in these hemodynamic variables are associated with life-threaten...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of Chronic Ethanol Feeding on Clonidine-Evoked Reductions in Blood Pressure, Heart Rate, and Their Variability: Time-Domain Analyses

El‐Mas

Abdel‐Rahman²

2003

J Pharmacol Exp Ther

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Behavioral and autonomic responses to intermittent social stress: differential protection by clonidine and metoprolol

1994

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The present study investigated physiological and pharmacological characteristics of socially "stressed" animals. Specifically, we examined (1) to what degree autonomic and behavioral "stress" reactions during intermittent confrontations between an intruder male adult Long-Evans rat with an aggressive resident undergo habituation, and (2) to what extent the defeat-experienced animal can be protected against these "stress" reactions with clonidine or metoprolol, two adrenergic agents with clinical anxiolytic effects. We developed an acute social stress situation that consisted of initially placing an experimental rat as an intruder into the homecage of a resident while the resident was not present, thereafter permitting brief physical agonistic interactions with the reintroduced resident until the intruder was forced into a submissive supine posture and emitted ultrasonic vocalizations (USV), and eventually exposing the intruder to the resident's threats for one hour, while being shielded from potentially injurious attacks ("threat encounter"). Over the course of the initial 4-weekly threat encounters the acute tachycardia but not the hyperthermic stress responses decreased in magnitude. Following the first three threat encounters core temperature (Tc) was significantly elevated for at least 3 h. The Tc was already elevated when the repeatedly defeated intruder was confronted with the olfactory cues of the resident's cage. This conditioned "anticipatory" hyperthermia developed in the course of the first three confrontations and was paralleled by a decrease in exploratory and motor behavior and by an increase in defensive behaviors and in both types of USV emitted in the "low" (20-30 kHz) and the "high" (31-70 kHz) frequency range. Clonidine (0.01-0.1 mg/kg, IP), an alpha 2-adrenergic agonist and metoprolol, a beta-adrenergic blocker (1.0-10.0 mg/kg, IP), dose-dependently prevented the tachycardic response to stress. Only clonidine, but not metoprolol, also attenuated the rise in Tc during the 1-h agonistic interaction. Clonidine decreased those aspects of motor behavior (e.g. rearing, walking) that are of lesser "cost" for the individual but maintained high levels of defensive reactions and increased the duration of "low" USV. The high doses of clonidine (0.06, 0.1 mg/kg) attenuated the homeostatic regulation and sedated the intruder while exposed to threats during a social confrontation. The absence of attenuation of the high level of defensive behavior and the prolonged "low" USV suggest a stress intensification by the higher doses of clonidine. In conclusion, after the fourth encounter, the autonomic, behavioral and vocal response pattern prior to and during repeated weekly confrontations show no evidence for habituation for the following 6 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

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Reduced plasma noradrenaline and abnormal heart rate variability in resting panic disorder patients

Middleton

Ashby

Robbins

1994

Biological Psychiatry

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Clonidine Reduces Blood Pressure and Heart Rate Oscillations in the Conscious Rat

Cited by 34 publications

References 0 publications

Effects of Chronic Ethanol Feeding on Clonidine-Evoked Reductions in Blood Pressure, Heart Rate, and Their Variability: Time-Domain Analyses

Effects of Chronic Ethanol Feeding on Clonidine-Evoked Reductions in Blood Pressure, Heart Rate, and Their Variability: Time-Domain Analyses

Behavioral and autonomic responses to intermittent social stress: differential protection by clonidine and metoprolol

Reduced plasma noradrenaline and abnormal heart rate variability in resting panic disorder patients

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