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

Abstract

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...

Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients

“…2 The dopaminergic (DAergic) influence on blood pressure regulation, including DAergic-mediated inhibition of norepinephrine (NE) at sympathetic neuroeffector endings, leads to a reduction of central and peripheral DAergic activity and a hypertensive condition, possibly accounting for essential hypertension. 3 Clinical studies show a DAergic modulation of sympathetic activity in hypertensive and obese individuals, 4 and DAergic agonists have been successfully used as a treatment for hypertension by reducing adrenergic neurotransmission at sympathetic endings. 5 As bromocriptine treatment in obese humans elicited a reduction of serum leptin values 6 and improved insulin sensitivity, 7 this indirectly suggests beneficial effects of reduced DAergic activity.…”

“…Evidence suggests that endogenous DA modulates NE synthesis and secretion in the noradrenergic neurons 25 and -at least in part -leptin release and OB gene expression in adipose tissue. As DAergic activity is reduced in subjects with hypertension and obesity, 3 this could explain in part that obesity, 26 sympathetic hyperactivity, 27 and hyperleptinemia 28 are associated with hypertension. We did not find effects of insulin on leptin release and OB gene expression in cultured adipocytes.…”

Poziom katecholamin w ślinie podczas stresu egzaminacyjnego i wysiłku poznawczego

“…Natomiast są one wykrywane w moczu, krwi oraz ślinie i wykorzystywane w diagnostyce nowotworów, a także zaburzeń funkcjonowania obwodowego układu nerwowego (Eisenhofer, Kopin, Goldstein 2004). Z kolei dopamina w części obwodowej organizmu jest produkowana zarówno przez układ nerwowy, jak i w poszczególnych tkankach, gdzie pełni funkcję przekaźnika parakrynowego, przekazując informacje między komórkami tylko lokalnie, w obrębie danej tkanki (Kuchel O., Kuchel G., 1991).…”

Peripheral dopamine in hypertension and associated conditions

“…With evolution towards terrestrial life, DA is opposing the catecholamine newcomers, the salt retaining NA and A. 6 In hypertension, the attenuated natriuretic response to both civilization acquisitions, salt and protein, due to NA and A overriding weakening DA responses, pin-points this level of inappropriate adaptation of man to modern lifestyle 22 as a contributor to hypertension.…”

“…The complexity of this system is further amplified by the dependence of multiple enzyme activities on previously summarised genetics, 3 environment and age. 6 The case for monitoring DA in hypertension can be made not only based on the biological action of DA itself but its mutual interactions with NA and A. The antagonistic physiological actions of DA and NA are mostly due to different receptor-mediated vasodilating-vasoconstrictor, natriuretic and antinatriuretic and their mutual release-modulating actions (eg, the presynaptic inhibition of NA release by DA).…”