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

Studies of cardiovascular risk factors in children conducted in the Bogalusa Heart Study provide a better understanding of the early natural history of essential hypertension. Contrasts in the biracial community of Bogalusa furnish some clues as to why essential hypertension is more prevalent in blacks. Black children tend to have higher blood pressure levels than whites. Autopsy studies and echocardiographic examinations have provided evidence of early cardiac enlargement in children and young adults with blood pressure levels in the 90th percentile. This suggests that the anatomic changes related to high blood pressure levels occur early in life. Blacks have lower plasma renin and serum dopamine beta-hydroxylase levels than whites. In general, obesity is not as closely correlated with higher blood pressure levels in black children as in white children. Prevention of hypertension should begin in early life. A major approach may be to educate children about cardiovascular risk factors and to encourage them to adopt healthy lifestyles while still young.
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PMID:Pathogenesis of hypertension in black and white children. 262 Apr 71

A possible mechanism of the previously observed increased adrenal dopamine release and tissue content in spontaneously hypertensive rats (SHR) was explored. The following changes in dopamine beta-hydroxylase activity and catecholamines were noted. At age four weeks (normotensive) or 12 weeks (hypertensive), SHR had lower dopamine beta-hydroxylase activity in the adrenals, heart ventricle and spleen than Wistar Kyoto rats. Tissue dopamine beta-hydroxylase activity in Wistar Kyoto rats was increased with age in the atria but decreased in the ventricles and did not change in the spleen. SHR also had reduced right heart atrial dopamine beta-hydroxylase activity in the hypertensive stage and an overall increase in atrial dopamine content even in the prehypertensive state compared to Wistar Kyoto rats. The increase in noradrenaline content seen with age in the right atrium and spleen in Wistar Kyoto rats was not found in SHR, possibly because of concomitantly decreased dopamine beta-hydroxylase activity. An augmented dopamine:noradrenaline ratio in the spleen of hypertensive SHR may also have been related to an abnormality of the synthesis of noradrenaline from dopamine not necessarily reflected by tissue dopamine beta-hydroxylase determination. A defect of beta-hydroxylation, partly attributable to deficient dopamine beta-hydroxylase activity, may thus precede hypertension and contribute to the hyperdopaminergic state found in SHR.
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PMID:A defective beta-hydroxylation of dopamine may precede the full development of hypertension in spontaneously hypertensive rats. 279 May 80

The dopamine beta-hydroxylase inhibitor SK&F 102698 was characterized by studying its cardiovascular effects in hypertensive rats. The antihypertensive effects of SK&F 102698 (50 mg/kg p.o.) were studied in three different rat models of hypertension. In spontaneously hypertensive and deoxycorticosterone acetate-salt rats SK&F 102698 produced blood pressure reductions of approximately 21 and 23%, respectively. In contrast, SK&F 102698 did not produce a significant decrease in blood pressure in 2-kidney, 1-clip Goldblatt hypertensive rats. The antihypertensive mechanism of action of dopamine beta-hydroxylase inhibition was probed with the selective DA1-receptor antagonist SCH 23390, which produced an attenuation of the antihypertensive effects of SK&F 102698. Experiments were designed to separate the peripheral from the central components of the cardiovascular effects of SK&F 102698. In spinal cord stimulated pithed spontaneously hypertensive rats, SK&F 102698 reduced blood pressure but not heart rate, indicating a peripherally mediated vasodilation and a centrally mediated heart rate effect. Furthermore, when SK&F 102698 was administered directly into the fourth ventricle of conscious spontaneously hypertensive rats, a pronounced bradycardia and lowering of blood pressure was observed. SCH 23390 (200 micrograms/kg i.v.) and l-sulpiride (1 mg/kg i.v.) inhibited the cardiovascular effects of SK&F 102698 administered into the fourth ventricle. These data indicate that inhibition of dopamine beta-hydroxylase with SK&F 102698 results in both peripherally and centrally mediated cardiovascular effects and suggest that central dopamine receptors contribute to the control of systemic blood pressure in hypertensive models associated with an increased sympathetic outflow.
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PMID:Further characterization of the cardiovascular effects of the dopamine beta-hydroxylase inhibitor SK&F 102698 in conscious hypertensive rats. 305 29

The current study tested the hypothesis that high NaCl diets elevate blood pressure in NaCl-sensitive spontaneously hypertensive rats (SHR-S) by reducing noradrenergic input to depressor neurons in the anterior hypothalamus. SHR-S were studied at 7 weeks of age, and age-matched salt resistant SHR (SHR-R) and normotensive Wistar-Kyoto rats (WKY) were controls. Rats were fed either high (8%) NaCl or control (1% NaCl) diets for 2 weeks, following which norepinephrine turnover in hypothalamus (anterior, posterior, and ventral regions), brainstem (pons and medulla), and thoracic spinal cord was assessed using the dopamine beta-hydroxylase inhibitor 1-cyclohexyl-2-mercapto-imidazole (CHMI). Regional brain catecholamines were measured by high performance liquid chromatography with electrochemical detection following intraperitoneal injection of CHMI or vehicle. Disappearance of norepinephrine following CHMI was used as an index of noradrenergic neuronal activity. The 8% NaCl diet caused a significant elevation in blood pressure in SHR-S but not in SHR-R or WKY. Endogenous norepinephrine levels and turnover were lower in the anterior hypothalamus of SHR-S fed 8% NaCl than in those fed 1% NaCl but were not significantly different in other groups. Endogenous norepinephrine levels and turnover were greater in pons of 8% NaCl--fed SHR-S than in those fed 1% NaCl but were not significantly different in other groups. These observations support the hypothesis that reduced noradrenergic input to depressor neurons in the anterior hypothalamus and increased noradrenergic input to neurons in the pons are related to NaCl sensitivity in the SHR-S.
Hypertension 1988 Jan
PMID:High NaCl diet reduces hypothalamic norepinephrine turnover in hypertensive rats. 333 40

The cardiovascular effects of a new class of potent inhibitors of dopamine beta-hydroxylase (DBH) were evaluated in spontaneously hypertensive rats (SHR). SK&F 102698 [1-(3,5-difluorobenzyl)imidazole-2-thiol] is the prototype molecule of this class of substituted 1-benzylimidazole-2-thiols and is one of the most potent inhibitors of DBH yet described. After acute p.o. administration in conscious unrestrained SHR, SK&F 102698 elicited a dose-dependent decrease in mean arterial blood pressure. The antihypertensive effect was marked by a gradual onset with long duration of activity. The antihypertensive effect produced by SK&F 102698 was accompanied by bradycardia. SK&F 102698 inhibited DBH in vivo as demonstrated by its ability to increase vascular levels of dopamine (DA) while concomitantly decreasing vascular levels of norepinephrine (NE), thus increasing the overall DA/NE ratio. The chronic cardiovascular effects of SK&F 102698 were evaluated in developing SHR. SHR were administered SK&F 102698 p.o. once daily for 9 weeks beginning when animals were 4 weeks of age. SK&F 102698 (50 mg/kg) significantly attenuated the development of hypertension of these SHR. Tolerance to the chronic effects of DBH inhibition was not observed and blood pressures in drug-treated animals were still reduced significantly 20 hr after drug administration. Vascular catecholamine levels were determined in the mesenteric artery of these chronically treated animals. Vascular DA levels were increased 290%, vascular NE levels were decreased 36% and the DA/NE ratio was increased 520%, as compared to controls. Furthermore, hearts weights of SHR receiving SK&F 102698 were approximately 10% lower than controls. The present study demonstrates that in SHR SK&F 102698 is an effective antihypertensive whose effects are mediated by the novel mechanism of DBH inhibition.
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PMID:Cardiovascular effects of a new potent dopamine beta-hydroxylase inhibitor in spontaneously hypertensive rats. 357 12

1-Aralkylimidazole-2-thiones have been shown to be potent multisubstrate inhibitors of dopamine beta-hydroxylase (DBH; EC 1.14.17.1). In the present study, a series of 1-benzylimidazole-2-thiones was prepared to explore the effects of substitution in the benzyl ring on the inhibition of DBH. A detailed structure-activity relationship for in vitro activity was discovered and this was shown by a modified Hansch analysis to correlate (r = 0.91) with four key structural features of the benzyl ring: the presence of a hydroxyl at the 4-position, molar refractivity at the 3-, 4-, and 5-positions, inductive effects of the substituents at the 3-, 4-, and 5-positions, and pi-electron density. The affinity (Kis) of eight substituted inhibitors for DBH was shown to correlate (r = 0.75) with the affinity (KD) of comparably substituted tyramines for the ternary DBH-oxygen-tyramine complex. This correlate is used to support the hypothesis that binding of inhibitor to DBH occurs in a fashion that mimics the binding of tyramine substrates. The most potent inhibitors were selected for study in vivo in the spontaneously hypertensive rat model of hypertension. The changes in vascular dopamine and norepinephrine levels that resulted from oral administration of the inhibitors corresponded to the observed reduction in mean arterial blood pressure. A divergence between in vitro potency and in vivo efficacy upon oral dosing was noted and is suggested to result from an in vivo metabolic conjugation of the phenolic group of inhibitor.
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PMID:Multisubstrate inhibitors of dopamine beta-hydroxylase. 2. Structure-activity relationships at the phenethylamine binding site. 382 Feb 19

Some metabolic consequences of experimental hypertension on rat brain capillaries and kidney glomeruli have been studied in rats made hypertensive by a combination of deoxycorticosterone acetate injection and elevated salt intake (DOCA-salt hypertension) and isoproterenol injection. Enzyme activities were studied in vitro to ascertain directly or indirectly any changes in the metabolism of catecholamines and prostaglandins, and lysosomal integrity under conditions of experimental hypertension. Experimental hypertension was accompanied by an elevation in the activities of aromatic L-aminoacid decarboxylase, dopamine beta-hydroxylase, and malondialdehyde concentration, both in the brain capillaries and kidney glomeruli of rats. On the other hand, monoamine oxidase activity increased in brain capillaries but decreased in kidney glomeruli. Acid phosphatase activity increased marginally in kidney glomeruli but decreased significantly in brain capillaries. The catecholamine-synthesizing potential appears to have been augmented in both the tissue capillaries with a compensatory increase in the degrading enzyme activity in the brain capillaries of hypertensive rats. The absence of such an increase and an actual decrease in the monoamine oxidase activity in the kidney glomeruli may be responsible for the sustained maintenance of the hypertensive state. Increased malondialdehyde concentration may be due to the stimulation of the prostaglandin metabolism by the augmented catecholamine metabolism.
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PMID:Aromatic L-amino acid decarboxylase, dopamine beta-hydroxylase, monoamine oxidase, malondialdehyde, and acid phosphatase in rat brain capillaries and kidney glomeruli in experimental hypertension. 400 39

Catecholamine levels and activity of catecholamine-forming enzymes have been quantitated in adrenal glands of Dahl sodium-resistant (R) and sodium-sensitive (S), genetically hypertensive rats maintained on low- or high-salt diets. A high-salt diet results in markedly different changes in the catecholamine metabolism in R and S rats. In R rats, a high-salt diet reduces the activities of tyrosine 3-hydroxylase (TH;-5%) and dopamine beta-hydroxylase (DBH; -18%) as well as the levels of all catecholamines (dopamine -28%, norepinephrine -11%, and epinephrine -28%). In contrast, S rats fed a high-salt diet showed increased TH (+7%) and phenylethanolamine N-methyltransferase (+16%) activities as well as an increased content of adrenal norepinephrine (+13%) and epinephrine (+21%). These findings demonstrate a genetic difference in the effects of a high-salt diet on the synthesis of catecholamines in the adrenal gland of Dahl R and S rats. Hypertension only occurs in S rats on a high-salt diet, concomitant with large increases in the formation of adrenal catecholamines.
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PMID:Increased adrenal catecholamines in salt-sensitive genetically hypertensive Dahl rats. 613 26

We have postulated that the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) are coded for by similar genes. To analyze the structural relationship of genes coding for these enzymes, we have cloned DNAs complementary (cDNA) to DBH and PNMT messenger RNAs (mRNAs). Using hybrid selection analysis to identify the cDNA clones positively, we discovered cross-hybridization between DBH cDNA clones and PNMT mRNA and between PNMT cDNA clones and DBH mRNA. Further analysis by RNA blot hybridization revealed that the DBH cDNA probe hybridized predominantly to a 5500 nucleotide mRNA and less strongly to a 1100 nucleotide species, and the PNMT cDNA probe hybridized strongly to the 1100 nucleotide mRNA and weakly to the 5500 nucleotide message. DNA blot hybridization analysis demonstrated that DBH and PNMT cDNA probes hybridized to several common restriction fragments of total cellular DNA. The evidence presented here suggests the existence of homologous gene-coding regions in DBH and PNMT cDNAs. These homologies may be the result of duplication of a common ancestral gene. DNA blot analysis suggests that these enzymes are coded for by single genes, which may be located in close proximity to each other in the DNA, and points to the existence of either a single gene or linked genes coding for all catecholamine enzymes.
Hypertension
PMID:Molecular biology of catecholamine neurons. Similar gene hypothesis. 614 99

The systemic, cardiovascular hemodynamic and biochemical interactions between clonidine and minoxidil were studied in ten patients with refractory and/or accelerated hypertension. Clonidine in oral doses of 150 to 900 micrograms/day decreased mean blood pressure (MAP) 18.6 mm Hg (p less than 0.01), average heart rate (HR) 16.4 bpm (p less than 0.01), limb blood flow 1.63 ml/100 g min (p less than 0.05), plasma renin activity (PRA) 1.13 ng/ml/hr (p less than 0.025), and urinary noradrenaline excretion rate 16.45 micrograms/24hr (p less than 0.05). Clonidine increased the preejection period index (PEPI) 12.4 msec ( p less than 0.001), but did not alter cardiac index (CI), total peripheral resistance index (TPRI), limb vascular resistance nor dopamine beta-hydroxylase activity. When minoxidil in oral doses of 5 to 22.5 mg was added, a further decrease in MAP of 24.2 mm Hg (p less than 0.01) was observed; PEPI decreased 20.6 msec (p less than 0.01), limb blood flow decreased 13.2 mm Hg/min 100 g/ml (p less than 0.05), and total peripheral resistance index decreased 13.3 mm Hg/min m2/L (p less than 0.05). Minoxidil increased average heart rate 8.2 bpm (p less than 0.05), PRA 1.68 ng/ml/hr (p less than 0.05) and urinary noradrenaline excretion rate 5.0 micrograms/24 hr (p less than 0.01). Limb blood flow, cardiac index and dopamine beta hydroxylase activity were not significantly altered by minoxidil. Neither clonidine nor minoxidil affected cardiovascular responses to treadmill exercise. We concluded that clonidine is a useful alternative agent to block a minoxidil-induced increase in sympathetic nervous activity.
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PMID:Cardiovascular hemodynamic interactions between clonidine and minoxidil in hypertensive patients. 633 28


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