Comparative Effects of Dopaminergic Agonists on Cardiovascular, Renal, and Renin‐Angiotensin Systems in Hypertensive Patients

Luchsinger, Augusta; Velasco, Manuel; Urbina, Adalberto; Morillo, J.; Romero, Eduardo; Álvarez, Rolando; Pieretti, Otto Hernandez

doi:10.1002/j.1552-4604.1992.tb03788.x

Cited by 21 publications

(16 citation statements)

References 22 publications

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“…Pramipexole had relatively minor effects on measures of nonpupillary autonomic functions (see Table 3). Both systolic and diastolic BP tended to be reduced in the standing position following drug administration, consistent with reports of a reduction in BP in response to dopamine receptor agonists [45–48]. Indeed, it has been reported that dopamine receptor agonists may cause orthostatic hypotension and subjective dizziness [8–12, 14, 46].…”

Section: Discussionsupporting

confidence: 84%

Comparison of pramipexole with and without domperidone co‐administration on alertness, autonomic, and endocrine functions in healthy volunteers

Samuels

Hou

Langley

et al. 2007

Brit J Clinical Pharma

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What is already known about this subject • It is known that the dopamine receptor agonist pramipexole, used for the treatment of Parkinson's disease, often causes nausea that can be treated in patients by the co‐administration of an antiemetic, for example domperidone. • In experimental studies of pramipexole it may be necessary to administer domperidone alongside pramipexole to alleviate nausea, and as such it is necessary to know how the co‐administration of domperidone may alter the observed effects of pramipexole. What this study adds • Results from our study indicate that the co‐administration of pramipexole and domperidone may reduce the likelihood of observing an effect that is present when pramipexole is administered alone. • Although domperidone is mainly a peripherally acting drug, it appears that a high enough concentration of the drug crosses the blood–brain barrier to partially antagonize some of the autonomic actions of pramipexole. • Therefore, this report provides a cautionary note to the use of domperidone alongside pramipexole where the results of interest are those from pramipexole alone. Aims To investigate the effects of the D2‐receptor agonist pramipexole with and without the co‐administration of the peripherally acting D2‐receptor antagonist domperidone on measures of alertness, autonomic and endocrine function. Methods Sixteen male volunteers participated in four weekly sessions of pramipexole 0.5 mg, domperidone 40 mg, their combination, and placebo administered according to a balanced, double‐blind design. Alertness (visual analogue scales (VAS), critical flicker fusion frequency, pupillographic sleepiness test), autonomic (pupil diameter, light and darkness reflexes, blood pressure, heart rate, salivation, temperature) and endocrine (prolactin, thyroid‐stimulating hormone (TSH), growth hormone (GH)) functions were assessed. Data were analyzed with anova with multiple comparisons. Results The pre‐post treatment changes in VAS alertness were reduced by pramipexole with and without domperidone (mean difference from placebo (95% confidence interval), mm): pramipexole −15.75 (−23.38, −8.13), combination −11.84 (−20.77, −2.91). Treatment condition significantly affected pupil diameter measured in different ways (resting pupil diameter (F3,45 = 8.39, P < 0.001), initial diameter of the light reflex response (F3,42 = 3.78, P < 0.05), and light (F3,45 = 5.21, P < 0.005) and dark (F3,45 = 3.36, P < 0.05) diameters of the darkness reflex response). Pramipexole without domperidone consistently increased pupil diameter on all measures (P < 0.05), whereas with domperidone only the increase in resting and dark diameters reached significance. Pramipexole reduced light reflex amplitude and increased latency, whereas the combination affected latency only. Concentrations of prolactin and TSH were increased by domperidone. Pramipexole reduced prolactin and increased GH concentrations. Conclusions The attenuation of the central pupillary effects of pramipexole by domperidone indicates that domperidone h...

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Section: Discussionsupporting

confidence: 84%

Comparison of pramipexole with and without domperidone co‐administration on alertness, autonomic, and endocrine functions in healthy volunteers

Samuels

Hou

Langley

et al. 2007

Brit J Clinical Pharma

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“…Bromocriptine‐QR (B‐QR), a quick‐release formulation of micronized bromocriptine, is the only sympatholytic dopamine‐agonist US FDA‐approved for the treatment of type 2 diabetes. In several preclinical and clinical studies, bromocriptine administration has repeatedly been demonstrated to reduce measures of elevated SNS activity such as reduction of elevated sympathetic outflow, plasma norepinephrine, BP and/or conversion of nondipper profile of circadian mean arterial pressure to a dipper profile. A critical aspect of dopaminergic control of autonomic function is via circadian modulation of the central biological clock pacemaker circuit (circadian neuronal afferent signals to and including the suprachiasmatic nuclei [SCN]) (see below).…”

Section: Introductionmentioning

confidence: 99%

Circadian‐timed quick‐release bromocriptine lowers elevated resting heart rate in patients with type 2 diabetes mellitus

Chamarthi

Vinik

Ezrokhi

et al. 2019

Endocrino Diabet & Metabol

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Objective: Sympathetic nervous system (SNS) overactivity is a risk factor for insulin resistance and cardiovascular disease (CVD). We evaluated the impact of bromocriptine-QR, a dopamine-agonist antidiabetes medication, on elevated resting heart rate (RHR) (a marker of SNS overactivity in metabolic syndrome), blood pressure (BP) and the relationship between bromocriptine-QR's effects on RHR and HbA1c in type 2 diabetes subjects.Design and Subjects: RHR and BP changes were evaluated in this post hoc analysis of data from a randomized controlled trial in 1014 type 2 diabetes subjects randomized to bromocriptine-QR vs placebo added to standard therapy (diet ± ≤2 oral antidiabetes medications) for 24 weeks without concomitant antihypertensive or antidiabetes medication changes, stratified by baseline RHR (bRHR). Results: In subjects with bRHR ≥70 beats/min, bromocriptine-QR vs placebo reduced RHR by −3.4 beats/min and reduced BP (baseline 130/79; systolic, diastolic, mean arterial BP reductions [mm Hg]: −3.6 [P = .02], −1.9 [P = .05], −2.5 [P = .02]). RHR reductions increased with higher baseline HbA1c (bHbA1c) (−2.7 [P = .03], −5 [P = .002], −6.1 [P = .002] with bHbA1c ≤7, >7, ≥7.5%, respectively] in the bRHR ≥70 group and more so with bRHR ≥80 (−4.5 [P = .07], −7.8 [P = .015], −9.9 [P = .005]). Subjects with bRHR <70 had no significant change in RHR or BP. With bHbA1c ≥7.5%, %HbA1creductions with bromocriptine-QR vs placebo were −0.50 (P = .04), −0.73 (P = .005) and −1.22 (P = .008) with bRHR <70, ≥70 and ≥80, respectively. With bRHR ≥70, the magnitude of bromocriptine-QR-induced RHR reduction was an independent predictor of bromocriptine-QR's HbA1c lowering effect. Conclusion:Bromocriptine-QR lowers elevated RHR with concurrent decrease in BP and hyperglycaemia. These findings suggest a potential sympatholytic mechanism contributing to bromocriptine-QR's antidiabetes effect and potentially its previously demonstrated effect to reduce CVD events. K E Y W O R D Sdopamine, sympathetic nervous system, type 2 diabetes

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“…1 It has been demonstrated that dopamine, a biogenic amine synthesized in different areas of the peripheral and central nervous systems, plays an important role in the regulation of central nervous, cardiovascular, renal, and endocrine systems through stimulation of a-and b-adrenergic receptors and the specific dopaminergic (DA 1 and DA 2 ) receptors. [2][3][4] A number of investigators have elucidated the role of dopamine in the pathogenesis and treatment of high blood pressure (BP). [3][4][5][6][7][8][9][10][11][12][13][14][15] Furthermore, it has been established that dopamine at dosages of 0.5 to 3 mg/kg/min is able to activate both dopaminergic receptors in the cardiovascular and renal systems.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] A number of investigators have elucidated the role of dopamine in the pathogenesis and treatment of high blood pressure (BP). [3][4][5][6][7][8][9][10][11][12][13][14][15] Furthermore, it has been established that dopamine at dosages of 0.5 to 3 mg/kg/min is able to activate both dopaminergic receptors in the cardiovascular and renal systems. Activation of dopaminergic receptors in the smooth muscle of arterioles induces vasodilatation, and in the kidney, dopamine regulates sodium excretion in renal tubules producing natriuresis, diuresis, increase in renal blood flow, and glomerular filtration.…”

Section: Introductionmentioning

confidence: 99%

Effect of Drugs Interacting With the Dopaminergic Receptors on Glucose Levels and Insulin Release in Healthy and Type 2 Diabetic Subjects

Contreras

Foullioux

Pacheco

et al. 2008

American Journal of Therapeutics

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Dopamine agonists play an important role in the regulation of the central nervous-cardiovascular, renal, and hormonal systems through stimulation of dopaminergic (DA1 and DA2) and alpha- and beta-adrenergic receptors. Several studies have shown that in fat and diabetic mice. The aim of the present study was to evaluate the interaction of the dopaminergic and endocrine systems by determining the effect of the dopaminergic antagonist, metoclopramide, and dopamine on insulin secretion and cardiovascular response by blockade and activation of dopamine receptors in healthy and type 2 diabetic subjects. Healthy subjects (n =15) and subjects with type 2 diabetes (n = 15) of both genders, aged 18 to 60 years, were recruited into this study. A comparative experimental design of 90 minutes was performed in which placebo (0.9% saline) was infused intravenously for the first 30 minutes followed by metoclopramide (7.5 microg/kg/min), a dopamine receptor antagonist for 30 minutes, and then metoclopramide (7.5 microg/kg/min) plus dopamine (0.5-3 microg/kg/min) for 30 minutes. The following clinical and biochemical parameters were measured at the beginning and then every 30 minutes of the experimental period (30', 60' and 90'): systolic-diastolic and mean arterial blood pressure, heart rate, serum glucose, insulin, triacylglycerides, and total cholesterol. Baseline glycosylated hemoglobin was measured and homeostasis model assessment for insulin resistance was calculated from insulin and glucose levels. Twelve-lead electrocardiograms were also obtained at these points. Dopamine infusion induced an increase in serum insulin, systolic blood pressure, and heart rate in healthy subjects but not in subjects with type 2 diabetes. Infusion of metoclopramide induced a hypotensive effect in healthy subjects, which was blunted by inclusion of dopamine in the infusion mixture. In subjects with diabetes, metoclopramide had no effect on blood pressure, but addition of dopamine raised systolic blood pressure. Neither metoclopramide nor dopamine altered significantly the lipid profile in healthy or diabetic subjects. Dopaminergic drugs increase serum insulin probably by interacting with dopaminergic receptors, but stimulation of beta-adrenergic receptors cannot be ruled out. Stimulation of cardiovascular dopamine receptors also caused modifications of hemodynamic parameters in healthy subjects, but apparently these receptors are attenuated in patients with type 2 diabetes probably as a result of endothelial dysfunction and alterations in the sympathetic nervous system sensitivity.

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Comparative Effects of Dopaminergic Agonists on Cardiovascular, Renal, and Renin‐Angiotensin Systems in Hypertensive Patients

Cited by 21 publications

References 22 publications

Comparison of pramipexole with and without domperidone co‐administration on alertness, autonomic, and endocrine functions in healthy volunteers

Comparison of pramipexole with and without domperidone co‐administration on alertness, autonomic, and endocrine functions in healthy volunteers

Circadian‐timed quick‐release bromocriptine lowers elevated resting heart rate in patients with type 2 diabetes mellitus

Effect of Drugs Interacting With the Dopaminergic Receptors on Glucose Levels and Insulin Release in Healthy and Type 2 Diabetic Subjects

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