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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

-Dopamine and angiotensin II (Ang II) receptors have been reported to exhibit an interaction in renal proximal tubules. The present study was designed to investigate the regulation by a D2-like dopamine receptor of Ang II-mediated stimulation of Na,K-ATPase activity in the renal proximal tubules. Ang II (10(-13) to 10(-9) mol/L) stimulated Na,K-ATPase activity in the proximal tubules that was completely abolished when the tubules were pretreated with the D2-like receptor agonist bromocriptine (1 micromol/L) for 30 minutes. The effect of bromocriptine on Ang II response was prevented by domperidone (1 micromol/L), a D2-like dopamine receptor antagonist. Similarly, the inhibition of forskolin (1 micromol/L)-induced cAMP accumulation caused by Ang II (10 pmol/L) was also abolished in bromocriptine-pretreated tubules. Basal and forskolin-stimulated cAMP was not significantly different in bromocriptine-treated tubules compared with the control. [3H]-Ang II binding sites (angiotensin type 1 [AT1] receptors) were reduced by approximately 65% in bromocriptine-treated proximal tubules, a result that was further substantiated by Western blot analysis revealing a 50% decrease in AT1 receptors in bromocriptine-treated tubules compared with the control. Western blot analysis of G proteins revealed a 2-fold increase in Gsalpha and a 20% decrease in Gialpha1 and Gialpha2 in the bromocriptine-treated proximal tubules. Bromocriptine (1 micromol/L) alone stimulated Na,K-ATPase activity during the first 30 minutes of incubation, and thereafter the stimulation fell to the basal level. Similarly, bromocriptine-mediated inhibition of cAMP lasted only up to 20 minutes. The data suggest that preactivation of D2-like dopamine receptors abolishes Ang II-mediated stimulation of Na,K-ATPase activity and inhibition of cAMP accumulation. This phenomenon may be a consequence of a decrease in AT1 receptors and alterations in G protein levels in the proximal tubules. We propose that such a regulation of Ang II response by bromocriptine is the result of heterologous desensitization of the D2-like receptor system.
Hypertension 1998 Dec
PMID:Bromocriptine regulates angiotensin II response on sodium pump in proximal tubules. 985 73

Dopamine plays an important role in the regulation of renal sodium excretion. The activation of D1-like receptors located on the proximal tubules causes inhibition of tubular sodium reabsorption by inhibiting Na,H-exchanger and Na,K-ATPase activity. The D1-like receptors are linked via G proteins to the multiple cellular signaling systems namely adenylyl cyclase and phospholipase C (PLC). A defective renal dopamine receptor function exists in spontaneously hypertensive rats (SHR). In the proximal tubules of SHR, the stimulation of adenylyl cyclase and PLC caused by dopamine was significantly reduced in comparison with Wistar-Kyoto (WKY) rats. Also unlike the effects seen in WKY, D1-like receptor activation did not inhibit Na,K-ATPase and Na,H-exchanger activities in SHR. In addition, reduced quantity of Gq/11alpha proteins was detected in the basolateral membranes of SHR compared to WKY rats. Studies revealed that there may be a primary defect in D1-like receptors leading to an altered signaling system in the proximal tubules and reduced dopamine-mediated effect on renal sodium excretion in SHR. Recently, it has been shown that the disruption of D1A receptors at the gene level causes hypertension in mice. Similar to SHR, dopamine and D1-like receptor agonist failed to inhibit Na,K-ATPase activity in the proximal tubules of old Fischer 344 rats. Unlike the observations in SHR where D1-like receptors were equal to WKY rats, there is a 50% decrease in D1-like receptor number in basolateral membranes of the old rats compared to the adult rats. Dopamine was unable to stimulate G proteins in the basolateral membranes of old rats compared to the adult rats. It is suggested that a defective dopamine receptors/signaling system may contribute to the development and maintenance of hypertension. Also, the inability of dopamine to inhibit Na,K-ATPase may lead to a reduced renal sodium excretion in response to dopamine in old rats.
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PMID:Renal dopamine receptor signaling mechanisms in spontaneously hypertensive and Fischer 344 old rats. 1005 39

The ability of the dopamine-1 (D1)-like receptor to stimulate adenylyl cyclase (AC) and phospholipase C (PLC), inhibit sodium transport in the renal proximal tubule (RPT), and produce natriuresis is attenuated in several rat models of hypertension. Since the inhibitory effect of D1-like receptors on RPT sodium transport is also reduced in some patients with essential hypertension, we measured D1-like receptor coupling to AC and PLC in cultures of human RPT cells from normotensive (NT) and hypertensive (HT) subjects. Basal cAMP concentrations were the same in NT (n=6) and HT (n=4). However, the D1-like receptor agonist fenoldopam increased cAMP production to a greater extent in NT (maximum response=67+/-1%) than in HT (maximum response=17+/-5%), with a potency ratio of 105. Dopamine also increased cAMP production to a greater extent in NT (32+/-3%) than in HT (14+/-3%). The fenoldopam-mediated increase in cAMP production was blocked by SCH23390 (a D1-like receptor antagonist) and by antisense D1 oligonucleotides in both HT and NT, indicating action at the D1 receptor. The stimulatory effects of forskolin and parathyroid hormone-related protein of cAMP accumulation were not statistically different in NT and HT, indicating receptor specificity and an intact G-protein/AC pathway. The fenoldopam-stimulated PLC activity was not impaired in HT, and the primary sequence and expression of the D1 receptor were the same in NT and HT. However, D1 receptor serine phosphorylation in the basal state was greater in HT than in NT and was not responsive to fenoldopam stimulation in HT. These studies demonstrate the expression of D1 receptors in human RPT cells in culture. The uncoupling of the D1 receptor in both rats (previously described) and humans (described here) suggests that this mechanism may be involved in the pathogenesis of hypertension; the uncoupling may be due to ligand-independent phosphorylation of the D1 receptor in hypertension.
Hypertension 1999 Apr
PMID:Dopamine-1 receptor coupling defect in renal proximal tubule cells in hypertension. 1020 44

1. Dopamine, via different dopamine receptor subtypes, regulates cardiovascular functions by actions on the central and peripheral nervous systems, vascular smooth muscle, the heart and the kidney. The dopaminergic system in the central nervous system (CNS) may participate in the regulation of systemic blood pressure. 2. Dopamine 'D2-like' (D2, D3 and D4) receptors, rather than 'D1-like' (D1 and D5) receptors, are involved in the CNS regulation of blood pressure; post-synaptic D2-like receptors increase blood pressure, while presynaptic D2-like receptors (the predominant action) produce the opposite effect. 3. Outside the CNS, dopamine may regulate blood pressure via pressure controls that act with intermediate rapidity (e.g. stress relaxation, arginine vasopressin and renin-angiotensin vasoconstriction), as well as those systems related to the long-term control of body fluid volume. 4. Dopamine D1- and D2-like receptors have been described in resistance vessels, such as the renal, mesenteric, coronary, pulmonary and cerebral arteries. The ability of D1-like receptors to inhibit renal smooth muscle hypertrophy indicates their importance in longer-term regulation of blood pressure. 5. Aberrant dopaminergic regulation of aldosterone secretion, via D2-like receptors, has been reported to be involved in some forms of hyperaldosteronism and hypertension. Some forms of hypertension may also be caused by an aberrant renal dopaminergic system. Abnormalities of three aspects of the renal dopaminergic system may lead to hypertension: (i) renal production of dopamine; (ii) transduction of the renal vascular dopamine signal; and (iii) transduction of the renal tubular dopamine signal. 6. Thus, increased blood pressure occurs after either blockade of D1-like receptors or of dopamine production in rats or disruption of the D1 receptor or the D3 receptor gene in mice.
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PMID:Role of dopamine in the pathogenesis of hypertension. 1038 48

Dopamine receptors type 2 (D2)-like receptor blockers cause an increase in the norepinephrine response to intense physical exercise. However, during intense physical exercise, D2-like antagonists also cause an increase in the epinephrine response, which itself might cause an increase in plasma norepinephrine through the activation of beta2 presynaptic receptors. Therefore, we evaluated the effect of domperidone, a D2-like antagonist, on the norepinephrine response to physical exercise in 6 Addison patients (3 were adrenalectomized and 3 had adrenal tuberculosis). In these patients, the norepinephrine increase observed during exercise was significantly higher after the administration of domperidone than a placebo (F=4,328; P<0.001). Because peripheral plasma norepinephrine does not reflect the sympathetic tone to the heart accurately, we evaluated the effect of domperidone administration (20 mg orally) on the sympathovagal balance, which was measured by the ratio between the high- and low-frequency components of heart rate variability, in 9 normal volunteers in the supine and sitting positions. When compared with placebo, domperidone caused a significant increase in the low/high frequency ratio (P<0.05) in the sitting position without modifying basal and stimulated norepinephrine plasma levels or blood pressure. These data support a role for endogenous dopamine in modulating norepinephrine release by human sympathetic nerves in vivo.
Hypertension 1999 Sep
PMID:In vivo evidence that endogenous dopamine modulates sympathetic activity in man. 1048 84

The present study examined renal dopaminergic activity and its response to high salt (HS) intake in adult (6-month-old) and old (24-month-old) Fischer 344 rats. Daily urinary excretion of L-3, 4-dihydroxyphenylalanine (L-DOPA), dopamine, and its metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid was similar in adult and old rats; by contrast, daily urinary excretion of norepinephrine in old rats was almost twice that in adult animals. HS intake (1% NaCl) over a period of 24 hours resulted in a 2-fold increase in the urinary excretion of dopamine, DOPAC, and norepinephrine in adult animals but not in old animals. Norepinephrine and L-DOPA plasma levels did not change during HS intake and were similar in both groups of rats. The natriuretic response to an HS intake in old rats (from 4.7+/-0.4 to 10.7+/-2.0 nmol. kg(-1). d(-1); Delta=6.0+/-0.9 nmol. kg(-1). d(-1)) was less than in adult rats (from 5.2+/-0.4 to 13.5+/-2.5 nmol. kg(-1). d(-1); Delta=8.3+/-0.8 nmol. kg(-1). d(-1)). A diuretic response to HS intake was observed in adult rats (from 20.9+/-2.3 to 37.6+/-2.8 mL. kg(-1). d(-1)) but not in old rats (from 37.7+/-5.7 to 42.3+/-6. 0 mL. kg(-1). d(-1)). Dopamine levels and dopamine/L-DOPA ratios in the renal cortex of old rats were greater than in adult rats. HS intake increased both dopamine levels and dopamine/L-DOPA ratios in the renal cortex of adult rats but not in old rats. Aromatic L-amino acid decarboxylase activity was higher in old rats than in adult rats; HS intake increased L-amino acid decarboxylase activity (nmol. mg protein(-1). l5 min(-1)) in adult rats (from 67+/-1 to 93+/-1) but not in old rats (from 86+/-2 to 87+/-2). Dopamine inhibited Na(+),K(+)-ATPase activity in proximal tubules obtained from adult rats, but it failed to exert such an inhibitory effect in old rats. It is concluded that renal dopaminergic tonus in old rats is higher than in adult rats but fails to respond to HS intake as observed in adult rats. This may be due in part to the inability of dopamine to inhibit Na(+),K(+)-ATPase activity in old rats.
Hypertension 1999 Oct
PMID:Aging, high salt intake, and renal dopaminergic activity in Fischer 344 rats. 1052 44

Some of the pathophysiological consequences of obesity include insulin resistance, increased renal sodium reabsorption, and the development of hypertension. Dopamine promotes renal sodium excretion via activation of D(1)-like receptors present on the proximal tubules. Reduced dopamine-induced natriuresis and a defect in D(1)-like receptor function have been reported in the proximal tubules of hypertensive animals. The present study investigated D(1)-like dopamine receptors and associated G proteins as the initial signaling components in the proximal tubular basolateral membranes of obese Zucker and control lean Zucker rats. We found that the obese rats were hyperinsulinemic, hyperglycemic, and hypertensive compared with the lean rats. Dopamine produced concentration-dependent inhibition of Na,K-ATPase activity in the proximal tubules of lean rats, whereas the inhibitory effect of dopamine was reduced in obese rats. The D(1)-like receptors measured by [(3)H]SCH 23390 binding revealed an approximately 45% decrease in B(max) without a change in K(d) in the basolateral membranes of obese rats compared with lean rats. Although we found an increase in G(q)/11alpha and no change in G(s)alpha in the basolateral membranes of obese rats, dopamine and SKF 38393 failed to stimulate G proteins as measured by [(35)S]GTPgammaS binding in obese rats, suggesting a receptor-G protein coupling defect. We conclude that decrease in D(1)-like dopamine receptor binding sites and diminished activation of G proteins, resulting perhaps from defective coupling, led to the reduced inhibition by dopamine of Na,K-ATPase activity in the proximal tubules of obese Zucker rats. Such a defect in renal dopamine receptor function may contribute to sodium retention and development of hypertension in obese rats.
Hypertension 1999 Nov
PMID:Defective dopamine receptor function in proximal tubules of obese zucker rats. 1056 87

Dopamine modulates cardiovascular function by actions in the central and peripheral nervous system, by altering the secretion/release of prolactin, pro-opiomelanocortin, vasopressin, aldosterone, and renin, and by directly affecting renal function. Dopamine produced by the renal proximal tubule exerts an autocrine/paracrine action via two classes of dopamine receptors, D1-like (D1 and D5) and D2-like (D2, D3, and D4), that are differentially expressed along the nephron. The autocrine/paracrine function of dopamine, manifested by tubular rather than by haemodynamic mechanisms, becomes most evident during extracellular fluid volume expansion. This renal autocrine/paracrine function is lost in essential hypertension and in some animal models of genetic hypertension. The molecular basis for the dopaminergic dysfunction in hypertension may involve an abnormal post-translational modification of dopamine receptors.
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PMID:D1 dopamine receptor signalling defect in spontaneous hypertension. 1069 8

Dopamine (DA) has been shown to influence kidney function through endogenous synthesis and subsequent interaction with locally expressed dopamine receptor subtypes (D1, D5 as D1-like and D2, D3, and D4 as D2-like). DA, and DA-receptor specific agonists and antagonists can alter renal water and electrolyte excretion along with renin release when infused systemically or intrarenally. Such effects are brought about by a combination of renal hemodynamic and direct tubular effects evoked along the full length of the nephron. The cellular mechanisms that direct these dopamine-mediated renal electrolyte fluxes have recently been clarified and include alterations in adenylyl cyclase, phospholipase C, and phospholipase A1 activity. The dopaminergic system also interacts directly with the renal kallikrein-kinin, prostaglandin and other neurohumoral systems. Aberrant renal dopamine production and/or dopamine receptor function have been reported in salt-dependent and low-renin forms of human primary hypertension as well as in genetic models of animal hypertension, including the SHR and Dahl SS rat. DA D1 or D3 receptor knockout mice have been shown to develop hypertension.
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PMID:Renal dopaminergic mechanisms and hypertension: a chronology of advances. 1080 30

Maintenance of a normal blood pressure requires a precise and fine-tuned regulation of salt metabolism. This is accomplished by a bidirectional regulation of renal tubular sodium transporters by natriuretic and antinatriuretic hormones. Dopamine, produced in the renal proximal tubular cells, plays an important role in this interactive system. Dopamine inhibits the activity of Na+,K+ ATPase as well as of many important sodium influx pathways in the nephron. These effects of dopamine are particularly pronounced in situation of sodium loading. There is an abundance of evidence suggesting that the natriuretic effects of ANP are to a large extent mediated via renal dopamine 1 like receptors. The renal tubular dopamine 1 like receptors are, under basal conditions, mainly located intracellularly. ANP and its second messenger, cGMP, cause a rapid translocation of the dopamine 1 like receptors to the plasma membrane. This phenomenon may explain how ANP and dopamine act in concert to regulate sodium metabolism. Regulation of sodium metabolism and blood pressure is critically dependent on a normal function of the renal dopamine system. Hence, abnormalities in the interaction between dopamine and ANP may predispose to hypertension.
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PMID:Mechanisms by which intrarenal dopamine and ANP interact to regulate sodium metabolism. 1080 35


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