Decreased Central Dopaminergic Activity in Essential Hypertension

Os, Ingrid; Kjeldsen, Sverre E.; Westheim, Arne; Aakesson, Ingvar; Norman, Nils; Enger, E; Hjermann, Ingvar; Eide, Ivar

doi:10.1097/00004872-198704000-00010

Cited by 20 publications

(21 citation statements)

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“…16 Some previous research has suggested that hypertension is associated with elevated basal prolactin concentration 17 and exaggerated prolactin response to the dopaminergic antagonist metaclopramide. 18,19 However, prolactin responses in individuals with a modest BP elevation in this study were blunted and therefore are inconsistent with a general increase in basal and stimulus-evoked prolactin release. Moreover, the prolactin responses in this study were adjusted for any covariation with baseline prolactin levels.…”

Section: Discussioncontrasting

confidence: 69%

Inverse Relationship Between Fenfluramine-Induced Prolactin Release and Blood Pressure in Humans

Muldoon

Sved²,

Flory³

et al. 1998

Hypertension

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Abstract-Although substantial evidence from experimental animals suggests that augmentation and reduction in serotonergic neurotransmission both affect arterial blood pressure (BP), it is unknown whether "tonic" central serotonergic activity is related to resting BP variability in humans. We tested this hypothesis in a community sample by evaluating the relationship between resting BP and a neuropharmacologic index of brain serotonergic activity (the fenfluramine challenge test). Subjects were 270 generally healthy men and women aged 25 to 60 years who were not receiving prescribed antihypertensive or psychotropic medications. The sample included 216 non-Hispanic whites and 47 blacks. Resting systolic BP ranged from 85 to 161 mm Hg and diastolic from 58 to 98 mm Hg. Each subject received 0.55 to 0.65 mg/kg D,L-fenfluramine hydrochloride, and the plasma prolactin concentration was measured over 3.5 hours. Analyses revealed a linear, inverse relationship between the maximum fenfluramine-induced prolactin rise and systolic and diastolic BP in whites: rϭϪ0.36 and rϭϪ0.29, respectively (PϽ0.001 for both). These relationships were not observed in the black participants. In whites, the prolactin response to fenfluramine remained a significant predictor of systolic and diastolic BPs in multivariate models including age, gender, body mass index, physical activity, smoking, and alcohol consumption (PՅ0.001). When compared with subjects in the highest quartile of prolactin response, individuals whose prolactin responses to fenfluramine comprised the lowest quartile were 2.6 times more likely to have a resting systolic/diastolic BP of Ͼ135/85 mm Hg. These data reveal that in white but not black adults, fenfluramine- Conversely, experimental manipulation of BP has also been found to influence serotonergic neural transmission in certain brain loci. However, it has never been demonstrated whether central serotonergic activity, under resting or basal conditions, is related to individual differences in BP.In the present study, central serotonergic activity was assessed with a neuroendocrine challenge with D,Lfenfluramine hydrochloride. Fenfluramine enhances serotonin neurotransmission by both inducing presynaptic release of serotonin stores and inhibiting synaptic reuptake.2,3 Activation of serotonergic receptors in the hypothalamus in turn promotes the pituitary release of prolactin into the circulation. Therefore, the rise in plasma prolactin concentration after fenfluramine administration reflects "net" serotonergic responsivity, as influenced by variability in presynaptic events (ie, synthesis, storage, release, and reuptake) and activation of hypothalamic 5-HT receptors. In this article we report an inverse correlation between interindividual variability in prolactin response to fenfluramine and resting BP that is independent of traditional risk factors for hypertension. Methods SubjectsThe 270 adult participants described in this report were recruited from the Pittsburgh area through media advertisements and local distrib...

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Section: Discussioncontrasting

confidence: 69%

Inverse Relationship Between Fenfluramine-Induced Prolactin Release and Blood Pressure in Humans

Muldoon

Sved²,

Flory³

et al. 1998

Hypertension

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“…Participants were included in this study if at baseline they had DBP between 94 and 105 mm Hg on two separate occasions. 15,16 The normotensive men (n ¼ 44) were recruited from the same population, that is, from the normotensive participants in The Oslo Study, and had blood pressure below 140/90 mm Hg. All 79 men had normal ocular fundi, electrocardiograms, urinalysis and kidney function estimated by creatinine clearance.…”

Section: Study Populationmentioning

confidence: 99%

“…15,16 All participants were examined in an outpatient setting by the same physicians. They were studied at the same time of day in a quiet room and at a constant room temperature.…”

Section: Study Protocol In 1984mentioning

confidence: 99%

Blood pressure development and hypertensive retinopathy: 20-year follow-up of middle-aged normotensive and hypertensive men

Gudmundsdottir¹,

Taarnhøj

Strand

et al. 2009

J Hum Hypertens

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Screening for hypertensive organ damage is important in assessing cardiovascular risk in hypertensive individuals. In a 20-year follow-up of normotensive and hypertensive men, signs of end-organ damage were examined, focusing on hypertensive retinopathy. In all, 56 of the original 79 men were reexamined for hypertensive organ damage, including by digital fundus photography. The diameters of the central retinal artery equivalent (CRAE) and vein were estimated and the artery-to-vein diameter ratio calculated. Components of metabolic syndrome were assessed. Fifty percent of the normotensive men developed hypertension during follow-up. Significant differences appeared in CRAE between the different blood pressure groups (P ¼ 0.025) while no differences were observed for other markers of hypertensive organ damage. There were significant relationships between CRAE and blood pressure at baseline (r ¼ -0.466, P ¼ 0.001) and at follow-up (r ¼ -0.508, Po0.001). A linear decrease in CRAE was observed with increasing number of components of the metabolic syndrome (b ¼ -3.947, R 2 ¼ 0.105, P ¼ 0.023). Retinal vascular diameters were closely linked to blood pressures and risk factors of the metabolic syndrome. The diversity in the development of hypertensive organ damage, with changes in retinal microvasculature preceding other signs of damage, should encourage more liberal use of fundus photography in assessing cardiovascular risk in hypertensive individuals.

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“…Since normal daily activities are punctuated by stimuli for peripheral sympathetic nervous activity (feeding, physical effort, and psychological stress), it is possible that a prolonged or more sustained response in the elderly induces a hyperadrenergic state, even under "normal" circumstances, 72 particularly in hypertension. It remains to be investigated to what degree a central dopaminergic deficiency, 127 complementary to that in peripheral dopaminergic mechanisms, may be involved in the pathogenesis of hypertension and in the interaction with other natriuretic and vasodilatory factors to overcome these evolutionary odds. Given the wellknown neurotransmitter role of DA in emotional and psychosocial interactions, clarification of this relation may represent an important contribution to our understanding as to why hypertension has emerged as such an important health problem at a time of spectacular industrial progress and human life extension when insecurity and psychosocial stimulation by suppressed anger 128 have replaced the physical stress to which primitive humans were exposed.…”

Section: Heterogeneity Of Dopamine's Involvement In Essential Hypertementioning

confidence: 99%

Peripheral dopamine in pathophysiology of hypertension. Interaction with aging and lifestyle.

Küchel

Kuchel

1991

Hypertension

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Dopamine, an ancestral catecholamine, is physiologically natriuretic and vasodilating, thus essentially protecting against hypertension. Its actions are overshadowed by the opposite effects of its main biological partner, norepinephrine, and this is accentuated with aging. Clinical observations combined with molecular biology approaches to catecholamine-synthesizing and catecholamine-metabolizing enzymes and receptors permit the identification of some inborn defects. Subtle changes in the dopamine-norepinephrine balance may account for the enhanced peripheral noradrenergic activity seen in the setting of decreased dopaminergic activity in advanced age. These changes may contribute to the diminished ability of the aged kidney to excrete a salt load, as well as to the finding that systolic blood pressure increases with age in populations with a high, but not in those with a low, intake of salt. The attainment of advanced age in Western societies with adverse lifestyle changes (mental rather than physical stress, excess salt intake, overeating, sedentarism) appears to facilitate the development of hyperten-sion. The adaptation to all the preceding lifestyle changes necessitates an increased dopamine generation, which may initially compensate to maintain appropriate natriuresis and vasodila-tion since many patients with initial borderline essential hypertension express their sympathetic hyperfunction, in addition to increased norepinephrine release, by excessive dopamine release. However, the progression of hypertension is accompanied by a peripheral dopaminer-gic deficiency and diminished ability to excrete salt. This may represent an eventual inadequacy of a phylogenetically redundant system resulting in decreased natriuresis and vasodilation and may account for the responsiveness of established chronic hypertension to salt restriction, diuretics, and dopaminomimetic medication. (Hypertension 1991;18:709-721) O ver the last decade, it has become apparent that dopamine (DA) is an important neuro-transmitter in the peripheral nervous system. Nonneuronal (kidney, intestine, blood vessels) and neuronal (neural terminals, adrenal medulla) tissues are target organs for circulating DA and also for DA synthesized and secreted locally as a paracrine substance. DA receptors located extracellularly in plasma-exposed cellular membranes transduce their signals to the intracellular milieu through a variety of second messengers, including adenylate cyclase, phos-pholipase C, protein kinase C, and other protein kinases. Peripheral DA! receptors (typical for vascular smooth muscles and renal tubules) act via adenylate cyclase and phospholipase C stimulation, whereas DA 2 receptors presynaptically suppress the release of norepinephrine (NE) via adenylate cyclase inhibition. 1 DA has been shown to affect the actions of ion transporters as well as a variety of cellular enzymes and appears to be physiologically important in the control of renal function. The sum of the effects of physiological DA concentrations on the kidney (DA r med...

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Decreased Central Dopaminergic Activity in Essential Hypertension

Cited by 20 publications

References 0 publications

Inverse Relationship Between Fenfluramine-Induced Prolactin Release and Blood Pressure in Humans

Inverse Relationship Between Fenfluramine-Induced Prolactin Release and Blood Pressure in Humans

Blood pressure development and hypertensive retinopathy: 20-year follow-up of middle-aged normotensive and hypertensive men

Peripheral dopamine in pathophysiology of hypertension. Interaction with aging and lifestyle.

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