Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A hypothesis is proposed admitting the participation of apometallothioneines (AMT) as a common link in the etiopathogenesis of hypertonic disease (HD) and some diseases with polygene heredity. The preconditions of the hypothesis are discussed (role of genetic disposition, external factors as salt, stress, tobacco smoking, alcohol, microelements--V and Cd and glucocorticoids in the origination of arterial hypertension). AMT homeostasis is discussed as well as the possible connection with the metabolism of Zn and Cu and Cu in organism. The chelating capacity of AMT makes it a potential regulatory protein, associated with the activity of Zn- and Cu-dependent enzymes and metalloenzymes. The mosaicism of pathology is explained with the genetic polymorphism of those enzymes (D beta H, MAO, etc), regardless of the common etiopathogenetic link. Some schemes are presented illustrating the hypothesis. The tendencies of the future studies are outlined in searching of direct proofs of the hypothesis.
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PMID:[Possible role of apometallothioneins]. 389 43

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

The complex mechanisms that maintain the blood pressure can be interfered with at many points by drugs. A drug acting at one point may be potentiated by another which blocks a compensatory reflex minimizing the effect of the first. Many therapeutically useful drug combinations have a nonspecific mechanism of this kind although drugs that act upon different points in the sympathetic efferent vasomotor pathway have not been proved to have a useful additive effect.It is not easy to prove a synergistic action of two drugs unless it is large. The best supported examples are combinations of either a diuretic or a vasodilator with a sympathetic blocking drug. These combinations are the ones most widely used in treatment of hypertension. They allow the dose of each active substance to be reduced so that unwanted side-effects are decreased without losing the desired action on the blood pressure.Drug combinations have special risks besides their obvious advantages. Patients are more likely to become confused and take the wrong doses if their treatment regime is complicated. Two drugs which are individually nontoxic may have dangers when used together. Oliguria and a mounting blood urea may follow combined use of powerful modern diuretics. Toxic effects may be entirely unrelated to the main therapeutic action of the drug, as with the enhanced diabetogenic effect of diazoxide used with hydrochlorothiazide.Several potent cardiovascular drugs modify the response to drugs which might be given to raise the blood pressure in an emergency. No drug in common therapeutic use seriously reduces the response to injected noradrenaline but some, such as sympathetic blockers and monoamine oxidase inhibitors, greatly increase sensitivity. Pressor amines that act indirectly by noradrenaline release may be ineffective in the presence of drugs which deplete or insulate the stores of the transmitter in adrenergic nerve endings.The advantages and disadvantages of drug interactions deserve more thought and study than they usually receive.
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PMID:Physiological and pharmacological interactions of antihypertensive drugs. 437 38

1. The degree of the decrease in the noradrenaline concentrations caused by 6-hydroxydopamine or immunosympathectomy was different in different areas of the cardiovascular system.2. In rats or guinea-pigs 6-hydroxydopamine depleted the noradrenaline content of the heart by 90%, of the mesenteric vein by 80% and of the mesenteric artery and aorta by 30-60%. Immunosympathectomy elicited a 70% reduction in the cardiac noradrenaline but only a 50% reduction in the noradrenaline of the blood vessels of the rat.3. The tyrosine hydroxylase activity of the heart, blood vessels, or adrenal glands was not significantly altered 2 weeks after 6-hydroxydopamine. Nor was the monoamine oxidase activity in heart or blood vessels changed.4. The inconsistent ability of both 6-hydroxydopamine and immunosympathectomy to abolish experimental hypertension may be due to the partial persistence of noradrenaline and functional sympathetic nervous system activity in the blood vessels.
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PMID:Resistance of noradrenaline in blood vessels to depletion by 6-hydroxydopamine or immunosympathectomy. 440 6

Two patients with severe postural hypotension associated with upper motor neuron and cerebellar impairment (Shy-Drager syndrome) have been studied. Head-up tilt and lower body negative pressure application caused marked falls in arterial pressure; in one patient, paradoxical vasodilatation was observed. Ice application did not increase arterial pressure or calculated forearm vascular resistance. Intravenous atropine in one patient increased heart rate by 18 beats per min, a cardioacceleratory response similar to exhausting recumbent exercise in that patient. 24 hr urinary catecholamine excretion was low, but aldosterone secretory rate was normal in the more severely afflicted patient. A prolonged elevation of plasma renin activity was noted when post-tilt hypertension occurred. When head-up tilt was not followed by this hypertensive period, plasma renin activity response to tilting was normal. Intra-arterial norepinephrine and tyramine both elicited a vasoconstrictor response. Intra-arterial infusions of norepinephrine and tyramine were repeated after administration of the monoamine oxidase inhibitor tranylcypromine. Norepinephrine was potentiated 4.1- and 0.5-fold in the two patients; tyramine was potentiated 3.7-and 1.1-fold in the two patients, respectively. A therapeutic program of tranylcypromine and tyramine (in the form of cheddar cheese) resulted in substantial clinical improvement. It is concluded that in at least some patients with idiopathic postural hypotension, norepinephrine is present in postganglionic sympathetic fibers. A therapeutic program of tyramine and a monoamine oxidase inhibitor may be of value when more conventional modes of therapy fail.
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PMID:Idiopathic postural hypotension: physiologic observations and report of a new mode of therapy. 543 69

To determine the effect of the duration and severity of hypertension on arterial wall metabolism 28 enzyme activities and several macromolecular complexes were histochemically studied in normotensive (WK), moderately (SHR) and strongly hypertensive (SP-SHR) rats at various ages. The results indicate that the abnormalities of 5' nucleotidase, acid esterase, cholinesterase and Alk.P. appeared in prehypertensive 4 w.old SHR. The posthypertensive changes, fluctuating in relation to the duration of hypertension, concerned: the pentose pathway, Krebs cycle and glycolosis -linked dehydrogenases; lysosomal enzymes; glycogen-phosphorylase and MAO; glycosaminoglycan and glycoprotein content. The structural and metabolic response presented several local and regional differences. The metabolic changes were greater in the aorta than in the caudal and femoral arteries. The comparison between SHR and SP-SHR indicates that the blood pressure (BP) at 170 mm Hg seems well tolerated during a long period of time. Severe lesions such as degeneration and failure of lipolytic activity in aortic smooth muscle cells (SMC), notable and early (8 mo.) in SP-SHR with 240 mm Hg were less intense and appeared later (13 mo.) in SHR with 190 mm Hg. The level of hypertension, rather than its duration, appears as a determining factor of posthypertensive vascular damage.
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PMID:Enzyme-histochemical changes in arteries of genetically hypertensive rats (SHR, SP-SHR). 632 44

Four sulfur-containing analogues of phenylpropylamine were synthesized and evaluated as substrates for dopamine beta-hydroxylase (DBH) and monoamine oxidase (MAO). All four phenyl aminoethyl sulfides were shown to be good substrates for DBH whereas only the two analogues not possessing a methyl group alpha to the terminal amino group were substrates for MAO. All four analogues were tested for acute antihypertensive activity in an animal model for hypertension, the spontaneously hypertensive rat (SHR). Two of the analogues, both of which should partition readily across the blood-brain barrier, did not appreciably reduce systemic blood pressure in the 6-h testing period. However, the two analogues that were designed to be relatively restricted to peripheral sites of action caused a dramatic drop in blood pressure in SHR of 25% within 1-1.5-h postinjection, with the analogue designed to be both restricted to the periphery and MAO inactive, causing a more prolonged antihypertensive activity.
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PMID:Antihypertensive activities of phenyl aminoethyl sulfides, a class of synthetic substrates for dopamine beta-hydroxylase. 648 71

The relationship between the onset of hypertension and changes in monoamine oxidase (MAO) activity in the brains and hearts of spontaneously hypertensive rats (SHR) were studied. After 7-weeks-old, blood pressure of SHR increased rapidly and reached a level of 170 to 180 mmHg; but following 4 weeks of propranolol treatment (10 mg/kg/day), blood pressure decreased significantly compared to that of untreated SHR. Heart/body weights ratio of SHR was higher than that of normotensive Wistar Kyoto rats (WKY). MAO activities in the brain stem, the medulla oblongata and pons of the SHR were significantly higher than those in WKY at 7 weeks of age, and MAO activity in the brain stem of the propranolol-treated SHR was significantly lower than that in the untreated SHR. Propranolol inhibited MAO activity in brain tissue in vitro, and the I50 values of propranolol were identical (1 X 10(-4) M) in SHR and WKY. In both the WKY strain and the SHR, the Vmax values of heart MAO increased with age, and the Vmax values of SHR were twice those of WKY. Km values for tyramine of heart MAO in WKY and SHR were approx. 100 microM and 140 microM, respectively; however, these values were not age-dependent. It was concluded that an increase in MAO activity in SHR brain stem may trigger a reduction in noradrenaline content and that propranolol may be responsible for its restoration, thus reducing peripheral sympathetic activity; moreover, the increase in MAO activity in the hearts of SHR may be of genetic origin.
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PMID:Hemodynamics and monoamine oxidase activity in spontaneously hypertensive rats (SHR). 664 13

The aim of our study was to investigate the activity of sympathetic nerves in arteries as a possible factor in the development of hypertension. In this paper, we report our results on the uptake of norepinephrine by the arteries of spontaneously hypertensive rats (SHR). Tail arteries of 7--9 week-old SHR and of normotensive controls (WKY) were incubated with [3H]norepinephrine for various periods of time. The 3H content in vessels of SHR and WKY was identical after 5 min but significantly higher in SHR after 15, 30, 60 and 90 min incubation. The rate of time-related uptake was greater in SHR as revealed by analysis of variance. The uptake of [3H]norepinephrine after 60 min was substantially less in vessels treated with cocaine in inhibit neuronal uptake or with desoxycorticosterone to inhibit extraneuronal uptake. After MAO activity was blocked with pargyline. 3H content remained higher in arteries of SHR than in those of WKY but after catechol-O-methyltransferase (COMT) was inhibited by U-0521, the difference was not significant. Our results demonstrate an alteration in the function of the sympathetic nerves in arteries as indicated by enhanced uptake of norepinephrine in the tail arteries of young SHR prior to the full development of hypertension.
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PMID:Norepinephrine uptake in arteries of spontaneously hypertensive rats. 665 85

Sixteen patients with refractory hypertension were treated with the monoamine oxidase inhibitor iproclozide at doses of 10 to 30 mg/day. Its addition to the previously prescribed antihypertensive therapy resulted in normalisation of blood pressure readings in two cases, significant improvement in seven cases and no change in four cases. Side effects due to iproclozide were relatively minor, the treatment having to be discontinued in three cases. Its association with alpha methyldopa or spironolactone did not lead to any untoward complications. Despite the success of other recently introduced drugs in refractory hypertension, this study shows that MAOI may be very useful in the management of this condition.
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PMID:[Treatment of certain refractory arterial hypertensions with a monoamine oxidase inhibitor]. 679 33


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