Yohimbine-precipitated clonidine withdrawal: An experimental model of the antihypertensive drug withdrawal syndrome

1992 ◽  
Vol 70 (6) ◽  
pp. 853-858 ◽  
Author(s):  
Donald H. Penning ◽  
Khem Jhamandas

In this study, a model of the clonidine withdrawal syndrome in normotensive rats was used to investigate the mechanisms and sites of the cardiovascular responses associated with this withdrawal. Clonidine (400 μg∙kg−1∙day−1), an α2-adrenergic receptor agonist, was administered to rats via indwelling osmotic minipumps for 7 days. Withdrawal was precipitated by an intravenous injection of the α2-adrenergic receptor antagonist yohimbine under α-chloralose anaesthesia, and the blood pressure and heart rate responses were recorded. Yohimbine (0.25, 0.50, and 1.0 mg/kg i.v.) in clonidine-treated rats provoked an immediate rise in blood pressure and heart rate. Similar injections in saline-treated rats produced slight hypotension and modestly increased the heart rate. Intracerebroventricular (i.c.v.) yohimbine injection (30 or 120 μg/kg in 10 μL volume) failed to elicit signs of withdrawal in clonidine-treated animals, but a subsequent intravenous injection of yohimbine (0.5 mg/kg) provoked brisk signs of withdrawal. Hexamethonium (2 mg/kg) pretreatment did not abolish the increase in the heart rate, but it delayed the blood pressure increase. Pretreatment with atropine sulfate (1 mg/kg) did not block the yohimbine-induced increase in heart rate or blood pressure. This study demonstrates that yohimbine can effectively produce cardiovascular signs of withdrawal in rats chronically exposed to clonidine. The lack of i.c.v. yohimbine suggests that the antagonist-precipitated withdrawal may not have a central origin. The failure of atropine to attenuate the blood pressure and heart rate responses, and the failure of hexamethonium to block the heart rate response and the late phase of blood pressure response, suggest that central cholinergic hyperactivity is not substantially involved in the yohimbine-precipitated clonidine withdrawal. It is suggested that under the conditions of clonidine exposure used here, the yohimbine-precipitated response may arise from increased activity of peripheral sympathetic mechanisms.Key words: yohimbine, clonidine withdrawal syndrome.

2021 ◽  
Author(s):  
Ko Yamanaka ◽  
Hidefumi Waki

Abstract In an environment of dynamically changing conditions, humans and animals can determine whether a current situation is favorable to them and accordingly select actions. Autonomic cardiovascular tuning is as important as motor control for this function. However, neuronal mechanisms underlying the dynamic adjustments of autonomic cardiovascular responses remain unclear. In this study, we hypothesized that the amygdala plays a role in autonomic cardiovascular tuning in a dynamically changing situation. We recorded the blood pressures and heart rates of head-restrained rats during appetitive and aversive classical conditioning tasks. Rats learned varying associations between conditioned stimuli and unconditioned stimuli in appetitive, neutral, and aversive blocks. Blood pressure and heart rate in the appetitive block gradually increased in response to reward-predicting cue, preceded by a vigorously increased response to the actual reward. The predictive response was significantly higher than the responses in the neutral and aversive condition blocks. Blood pressure and heart rate responses to the air puff-predicting cue in the aversive block were significantly lower than that of the responses in the neutral block. The conditioned blood pressure response rapidly changed through condition switching. Furthermore, bilateral pharmacological inactivation of the central nucleus of the amygdala has significantly decreased reward-predictive pressor responses in the latter phase, but not in the initial phase of block change. These results suggest that blood pressure is adaptively tuned by positive and negative conditioned stimuli and that the central nucleus of the amygdala likely assists in maintaining pressor response in dynamically changing situations.


Author(s):  
Pedro Augusto Carvalho Mira ◽  
Maria Fernanda Almeida Falci ◽  
Janaína Becari Moreira ◽  
Rosa Virginia Diaz Guerrero ◽  
Tarsila Campanha da Rocha Ribeiro ◽  
...  

We sought to test the hypothesis that the cardiovascular responses to isolated muscle metaboreflex activation would be blunted in patients with cirrhosis. Eleven patients with cirrhosis and 15 healthy controls were evaluated. Blood pressure (BP, oscillometric method), contralateral forearm blood flow (FBF, venous occlusion plethysmography) and heart rate (HR, electrocardiogram) were measured during baseline, isometric handgrip at 30% of maximal voluntary contraction followed by post-exercise ischemia (PEI). Forearm vascular conductance (FVC) was calculated as follows: (FBF/mean BP) x 100. Changes in HR during handgrip were similar between groups, but tended to be different during PEI (controls: ∆0.5 ± 1.1 bpm vs. cirrhotic patients: ∆3.6 ± 1.0 bpm, P = 0.057). Mean BP response to handgrip (controls: ∆20.9 ± 2.7 mmHg vs. cirrhotic patients: ∆10.6 ± 1.5 mmHg, P = 0.006) and PEI was attenuated in cirrhotic patients (controls: ∆16.1 ± 1.9 mmHg vs. cirrhotic patients: ∆7.2 ± 1.4 mmHg, P = 0.001). In contrast, FBF and FVC increased during handgrip and decreased during PEI similarly between groups. These results indicate that an abnormal muscle metaboreflex activation explained, at least partially, the blunted pressor response to exercise exhibited by cirrhotic patients. Novelty bullets: • Patients with cirrhosis present abnormal muscle metaboreflex activation • Blood pressure response was blunted, but forearm vascular response was preserved • Heart rate response was slightly elevated


Author(s):  
Ewan Thomas ◽  
Marianna Bellafiore ◽  
Ambra Gentile ◽  
Antonio Paoli ◽  
Antonio Palma ◽  
...  

AbstractThe aim of this study will be to review the current body of literature to understand the effects of stretching on the responses of the cardiovascular system. A literature search was performed using the following databases: Scopus, NLM Pubmed and ScienceDirect. Studies regarding the effects of stretching on responses of the cardiovascular system were investigated. Outcomes regarded heart rate(HR), blood pressure, pulse wave velocity (PWV of which baPWV for brachial-ankle and cfPWV for carotid-femoral waveforms), heart rate variability and endothelial vascular function. Subsequently, the effects of each outcome were quantitatively synthetized using meta-analytic synthesis with random-effect models. A total of 16 studies were considered eligible and included in the quantitative synthesis. Groups were also stratified according to cross-sectional or longitudinal stretching interventions. Quality assessment through the NHLBI tools observed a “fair-to-good” quality of the studies. The meta-analytic synthesis showed a significant effect of d=0.38 concerning HR, d=2.04 regarding baPWV and d=0.46 for cfPWV. Stretching significantly reduces arterial stiffness and HR. The qualitative description of the studies was also supported by the meta-analytic synthesis. No adverse effects were reported, after stretching, in patients affected by cardiovascular disease on blood pressure. There is a lack of studies regarding vascular adaptations to stretching.


1985 ◽  
Vol 69 (5) ◽  
pp. 533-540 ◽  
Author(s):  
Gianfranco Parati ◽  
Guido Pomidossi ◽  
Agustin Ramirez ◽  
Bruno Cesana ◽  
Giuseppe Mancia

1. In man evaluation of neural cardiovascular regulation makes use of a variety of tests which address the excitatory and reflex inhibitory neural influences that control circulation. Because interpretation of these tests is largely based on the magnitude of the elicited haemodynamic responses, their reproducibility in any given subject is critical. 2. In 39 subjects with continuous blood pressure (intra-arterial catheter) and heart rate monitoring we measured (i) the blood pressure and heart rate rises during hand-grip and cold-pressor test, (ii) the heart rate changes occurring during baroreceptor stimulation and deactivation by injection of phenylephrine and trinitroglycerine, and (iii) the heart rate and blood pressure changes occurring with alteration in carotid baroreceptor activity by a neck chamber. Each test was carefully standardized and performed at 30 min intervals for a total of six times in each subject. 3. The results showed that the responses to any test were clearly different from one another and that this occurred in all subjects studied. For the group as a whole the average response variability (coefficient of variation) ranged from 10.2% for the blood pressure response to carotid baroreceptor stimulation to 44.2% for the heart rate response to cold-pressor test. The variability of the responses was not related to basal blood pressure or heart rate, nor to the temporal sequence of the test performance. 4. Thus tests employed for studying neural cardiovascular control in man produce responses whose reproducibility is limited. This phenomenon may make it more difficult to define the response magnitude typical of each subject, as well as its comparison in different conditions and diseases.


1963 ◽  
Vol 18 (5) ◽  
pp. 987-990 ◽  
Author(s):  
Shanker Rao

Reports of cardiovascular responses to head-stand posture are lacking in literature. The results of the various responses, respectively, to the supine, erect, and head-stand posture, are as follows: heart rate/min 67, 84, and 69; brachial arterial pressure mm Hg 92, 90, and 108; posterior tibial arterial pressure mm Hg 98, 196, and 10; finger blood flow ml/100 ml min 4.5, 4.4, and 5.2; toe blood flow ml/100 ml min 7.1, 8.1, and 3.4; forehead skin temperature C 34.4, 34.0 and 34.3; dorsum foot skin temperature C 28.6, 28.2, and 28.2. It is inferred that the high-pressure-capacity vessels between the heart level and posterior tibial artery have little nervous control. The high-pressure baroreceptors take active part in postural adjustments of circulation. The blood pressure equating mechanism is not as efficient when vital tissues are pooled with blood as when blood supply to them is reduced. man; heart rate; blood flow; skin temperature Submitted on January 3, 1963


2016 ◽  
Vol 29 (3) ◽  
pp. 543-552
Author(s):  
João Douglas Alves ◽  
Jorge Luiz de Brito Gomes ◽  
Caio Victor Coutinho de Oliveira ◽  
José Victor de Miranda Henriques Alves ◽  
Fabiana Ranielle de Siqueira Nogueira ◽  
...  

Abstract Introduction: Tai-Chi-Chuan and Yoga have becoming popular practices. However is unclear the cardiovascular effects, and if they present similar behavior to aerobic and resistance sessions. Objective: To evaluate the cardiovascular responses during the session and post-exercise hypotension (PEH) of Tai Chi Chuan (TS) and Yoga (YS) in comparison to aerobic (AS) and resistance (SR) exercises. Methods: Fourteen young women (22.3 ± 2 years) apparently healthy performed four sessions (AS, RS, TS and YS). The heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) were recorded at resting, during (every 10 minutes) and until 50 minutes of recovery. Results: AS, RS, TS e YS showed significant increase in HR compared to resting.AS at 10, 30 e 50 minutes in relation to RS, TS e YS. The RS in relation to TS and YS at 10, 30 and 50 minutes. No significant difference between TS and YS. SBP was significantly increased in AS, RS, TS e YS at 10, 30 e 50 minutes during the session, in relation to rest. AS was significantly higher at 30 e 50 minutes than RS and higher than TS and YS at 10, 30 e 50 minutes. No significant difference in DBP. For PEH, AS, RS and TS significantly reduced at 10, 30 and 50 minutes. YS reduced at 50 minutes. No significant diastolic PEH. Conclusion: TS and YS showed as safe alternatives of exercising in the normotensive young adult woman, despite having lower values, they promote similar hemodynamic behavior to AS and RS.


2010 ◽  
Vol 108 (6) ◽  
pp. 1591-1594 ◽  
Author(s):  
Scott L. Davis ◽  
Craig G. Crandall

The Valsalva maneuver can be used as a noninvasive index of autonomic control of blood pressure and heart rate. The purpose of this investigation was to test the hypothesis that sympathetic mediated vasoconstriction, as referenced by hemodynamic responses during late phase II (phase IIb) of the Valsalva maneuver, is inhibited during whole body heating. Seven individuals (5 men, 2 women) performed three Valsalva maneuvers (each at a 30-mmHg expiratory pressure for 15 s) during normothermia and again during whole body heating (increase sublingual temperature ∼0.8°C via water-perfused suit). Each Valsalva maneuver was separated by a minimum of 5 min. Beat-to-beat mean arterial blood pressure (MAP) and heart rate were measured during each Valsalva maneuver, and responses for each phase were averaged across the three Valsalva maneuvers for both thermal conditions. Baseline MAP was not significantly different between normothermic (88 ± 11 mmHg) and heat stress (84 ± 9 mmHg) conditions. The change in MAP (ΔMAP) relative to pre-Valsalva MAP during phases IIa and IIb was significantly lower during heat stress (IIa = −20 ± 8 mmHg; IIb = −13 ± 7 mmHg) compared with normothermia (IIa = −1 ± 15 mmHg; IIb = 3 ± 13 mmHg). ΔMAP from pre-Valsalva baseline during phase IV was significantly higher during heat stress (25 ± 10 mmHg) compared with normothermia (8 ± 9 mmHg). Counter to the proposed hypothesis, the increase in MAP from the end of phase IIa to the end of phase IIb during heat stress was not attenuated. Conversely, this increase in MAP tended to be greater during heat stress relative to normothermia ( P = 0.06), suggesting that sympathetic activation may be elevated during this phase of the Valsalva while heat stressed. These data show that heat stress does not attenuate this index of vasoconstrictor responsiveness during the Valsalva maneuver.


1987 ◽  
Vol 62 (3) ◽  
pp. 1186-1191 ◽  
Author(s):  
J. W. Kozelka ◽  
G. W. Christy ◽  
R. D. Wurster

The ascending spinal pathways mediating somatocardiovascular reflexes during exercise were studied in unanesthetized dogs by placing lesions in the lumbar spinal cord. After training to run on a treadmill with hindlimbs only, 20 dogs were anesthetized and instrumented using sterile surgical techniques. To chronically record heart rate and arterial blood pressure, the aorta was cannulated via the omocervical artery. To test the intactness of descending spinal sympathetic pathways, reflex pressor responses to baroreceptor hypotension were produced by bilateral carotid arterial occlusion using pneumatic vessel occluders placed around the common carotid arteries. To generate transient ischemic exercise (120 s), a pneumatic occluder was placed around the left iliac artery. Eight to 10 days after instrumentation, blood pressure and heart rate were monitored at rest and during hindlimb running with and without simultaneous iliac arterial occlusion. The modest pressor response and tachycardia elicited by hindlimb exercise were markedly augmented by simultaneous hindlimb ischemia (i.e., iliac arterial occlusion). Lesion placement in the dorsolateral sulcus area and the dorsolateral funiculus at L2 significantly reduced the blood pressure and heart rate responses to simultaneous exercise occlusion. The cardiovascular responses to nonischemic exercise and bilateral carotid arterial occlusion were not altered by such spinal sections. It is concluded that in the dog the ascending spinal pathways mediating cardiovascular responses to ischemic exercise are located in the lateral funiculus, including the dorsolateral sulcus area and dorsolateral funiculus.


1997 ◽  
Vol 94 (21) ◽  
pp. 11589-11594 ◽  
Author(s):  
A. Cavalli ◽  
A.-L. Lattion ◽  
E. Hummler ◽  
M. Nenniger ◽  
T. Pedrazzini ◽  
...  

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