UMLS:C0020538 - FACTA Search

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

A case of anesthesia for a heart-transplant operation on a patient on mono-amine oxidase inhibitors (M.A.O.I.) is reported. This 63-year-old farmer was in end-stage cardiac failure due to familial cardiomyopathy. For 24 hours before surgery, he was on a dobutamine infusion (3 mcg/kg/min). He had been taking nialamide (100 mg/day) for 8 years for reactional depression and had not stopped it, despite advice. Anesthesia was induced with etomidate and succinylcholine, and maintained with fentanyl (25 mcg/kg/min) and pancuronium. Cardio-vascular stability was maintained during induction and first stage of surgery, up to cardectomy. Graft ischemia was 188 minutes. Successful defibrillation occurred after verapamil 3 mg. Weaning from C.P.B. was easy with dopamine (5 mcg/kg/min) and isoprenaline (0.01 mcg/kg/min). Post-operatively, on day 1, hypertension appeared and needed a nitroprusside infusion. On day 3, the patient needed another anesthetic for removal of pericardial clots, without problems. He remained very confused and disorientated during all his stay in hospital, but improved greatly with a neuroleptic. He left the hospital on day 28 in a good shape, with an anxiolytic, captopril and immunosuppressors. One month later, he was back on nialamide. The pharmacology of the M.A.O.I. is reviewed and their interactions with anesthesia are discussed as well as the use of inotropes. In this case, the denervated heart-graft, free from M.A.O. inhibition, behaved normally when transplanted in a chronically M.A.O.I. treated recipient.
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PMID:Heart-transplant and mono-amine oxidase inhibitors. 280 Sep 99

A patient with acute necrosis of the intestinal mucosa and high serum diamine oxidase activity is described. The 71-year-old woman, with a history of hypertension and cardiovascular and peripheral arteriosclerotic disease, presented with acute epigastric pain, vomiting, and a deteriorating hemodynamic condition. Serum level of the intestinal enzyme diamine oxidase (DAO) obtained on admission, approximately 24 hr after the onset of symptoms, was 7.4 times above the normal value. An exploratory laparotomy performed 6 hr later revealed cyanosis and areas of transmural necrosis involving the entire small bowel. The bowel was not resected because of the extent of lesion. Thirty hours after the first sample was taken and 2 hr before death, the serum DAO level was only slightly above normal. It is suggested that this biochemical marker could provide a valuable tool for the early diagnosis of intestinal ischemia.
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PMID:Acute necrosis of the intestinal mucosa with high serum levels of diamine oxidase. 643 1

We have developed a model of aortic smooth muscle necrosis in adult Sprague Dawley rats by feeding them two vascular toxins (allylamine HCl, or AA, and beta-aminopropionitrile, or betaAPN) in concert for 10 days. Either toxin given alone does not cause aortic lesions. In order to shed light on the mechanism of the synergistic action of these two toxins we fed known modulators of AA or betaAPN toxicity to rats concurrently with the two toxins. As modulators we used (a) semicarbazide (98 mg/kg/day, given 4 h prior to toxins), a known inhibitor of the vascular enzyme SSAO which metabolizes AA; (b) L-cysteine (1.5% in rat chow, beginning 3 days prior to toxins), which has been shown to reduce the toxic effects of betaAPN; and (c) phenelzine sulphate (3 mg/kg/day, given 4 h prior to toxins), an inhibitor of SSAO and potentiator of betaAPN toxicity. Rats were fed various combinations of the toxins and modulators by gavage: water (n = 8); (AA, 100 mg/kg/day) AA + phenelzine (n = 8); AA + semicarbazide (n = 8); AA + L-cysteine (n = 11); (betaAPN, 1 g/kg/day) betaAPN + phenelzine (n = 8); betaAPN + semicarbazide (n = 8); betaAPN + L-cysteine (n = 8); (AA, 100 mg + betaAPN, 1 g/kg/day) AA + betaAPN + phenelzine (n = 9), AA + betaAPN + semicarbazide (n = 8); AA + betaAPN + L-cysteine (n = 12); phenelzine (3 mg/kg/day) (n = 4); semicarbazide (98 mg/kg/day) (n = 4) and L-cysteine (1.5% in rat chow) (n = 4). We found that phenelzine sulphate (a drug previously used in the treatment of hypertension) when given with AA reproduced the AA + betaAPN induced aortic lesions. Phenelzine + betaAPN caused no lesions, but when combined with AA + betaAPN, aortic lesions were intensified and included marked secondary degeneration of the vascular wall. Semicarbazide was found to completely obviate the vascular toxicity of AA + betaAPN. L-Cysteine feeding markedly decreased the incidence and severity of vascular lesions in AA + betaAPN treated rats, but did not change the incidence or severity of heart lesions caused by AA alone. These data indicate that the synergistic necrotizing toxicity of AA + betaAPN is primarily an AA effect. We postulate that some modulating influence of betaAPN (or phenelzine) on tissue distribution, metabolism, or detoxification pathways of AA increases AA's acute vascular toxicity, whereas semicarbazide offers protection by inhibiting the initial deamination of AA to a highly reactive aldehyde.
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PMID:Allylamine and beta-aminopropionitrile induced aortic medial necrosis: mechanisms of synergism. 957 Mar 26

Pharmacological interaction is identified among other aspects when the effects of a drug are significantly altered clinically by the presence of food. The most important clinical significance in the history of drug-food interactions occurred in the fifties, the vitamin B6 deficiency when administering the tuberculostatic isoniazide, but there is no doubt that the interaction in the sixties between drugs that were inhibitors of the enzyme mono-amine oxidase and the biogenic amines tyramine and histamine had an important clinical significance due to the increase in hypertension and deaths due to cerebro-vascular accidents. In the seventies the types of interactions were due to the chelation between tetracyclines and the calcium of milk products, influencing the bioavailability of the antibiotic, and from this point on, studies explore in depth the interaction of foods with the different steps in the pharmacokinetics of the drugs (absorption, distribution, metabolization, and excretion), and these have helped to explain the metabolization interactions of drugs like the clinical significance between grapefruit juice whose naringenine flavonoid is a powerful inhibitor of cytochrome 450, particularly the CYP3A4 family, and terfenadine (antihistamine), with an increase in the plasma levels of the drug and patient death due to ventricular arrhythmia. In the USA the Joint Commission on Accreditation of Health Care Organization (JCAHO) has recommended monitoring of the possible drug and food interactions since 1985, and recommends that patients be informed of this. Despite the recommendations of the JCAHO, few American hospitals have protocolized these interactions and even fewer comply with these, and according to some authors, this is due to the lack of motivation caused by the lack of clinical significance. In this chapter we will study the effect of foods on drugs in two aspects: at the pharamcokinetic level with the possible alterations in absorption, distribution, metabolization, and excretion, and at the pharamcodynamic level, by alterations in the action of the drug. Also, based on a study by Delgado, which we have changed somewhat, we will report how the drugs should be taken to avoid interactions with foods. As a conclusion, it is difficult to establish which are the relevant drug-food interactions, unless they have given clinical problems. The following are important: a) drugs with a narrow therapeutic margin in which an absorption problem or a metabolization problem may disrupt the plasma levels and the patient needs (digoxin, teophylline, cyclosporin, etc). And b) the drugs like some antibiotics that, because of their action mechanisms, need to maintain adequate plasma concentrations.
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PMID:[Drug-food interactions]. 1054 35

The vascular response to most neurotransmitters of different vascular beds is altered under hypertensive condition. The modulatory effect of genetic pulmonary arterial hypertension on histamine responses is not known. The present study was undertaken to evaluate the modulatory effect of enzymatic degradation (via histamine N-methyl-transferase and diamine oxidase) on the vascular response of histamine, and the subtype(s) of histamine receptor present in the pulmonary artery (first branch, O.D. approximately 800 microm) of the normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) (male, 22-26 weeks old). In phenylephrine (1 microM) pre-contracted preparations, histamine and 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT, a histamine H(1) receptor agonist) elicited a concentration-dependent relaxation, with a smaller magnitude recorded in SHR. Application of 10 microM S-[4-(N,N-dimethylamino)-butyl]isothiourea (SKF 91488, a selective histamine N-methyl-transferase inhibitor), but not aminoguanidine (100 microM, a diamine oxidase inhibitor), significantly attenuated histamine-induced relaxation. Clobenpropit (1 nM, a potent histamine H(3) receptor antagonist) "antagonised" the suppressive effect of SKF 91488 and histamine-evoked relaxation was restored. Endothelial denudation reduced histamine- and abolished HTMT-elicited relaxation. Dimaprit (a histamine H(2) receptor agonist) caused an endothelium-independent, cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL 12330A, 10 microM, an adenylate cyclase inhibitor)-sensitive, concentration-dependent relaxation, with a similar magnitude in both strains of rat. Histamine-evoked relaxation was reversed into a further contraction (clobenpropit (10 nM)-sensitive) (with a greater magnitude occurred in the WKY rat) after blocking the histamine H(1) and H(2) receptors with diphenhydramine plus cimetidine (30 microM each). A similar further contraction (clobenpropit-sensitive) was observed with imetit (a histamine H(3)/H(4) receptor agonist) (> or =3 microM). Under resting tension, imetit (> or =0.3 microM) caused a clobenpropit (10 nM)- and prazosin (1 microM)-sensitive, concentration-dependent contraction, with a greater contraction in the WKY rats. Our results suggest that inhibition of histamine catabolism using SKF 91488 (histamine N-methyl-transferase inhibitor) resulted in a reduction of histamine-mediated relaxation that was due to the activation of the clobenpropit-sensitive, histamine H(3)/H(4) receptor and the release of catecholamine. In addition, activation of histamine H(1) and H(2) receptors resulted in relaxation whereas histamine H(3)/H(4) receptor activation by imetit yielded a prazosin-sensitive contraction of the pulmonary artery.
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PMID:An in vitro study of histamine on the pulmonary artery of the Wistar-Kyoto and spontaneously hypertensive rats. 1278 30

Increased risk of vasospasm, a spontaneous hyperconstriction, is associated with atherosclerosis, cigarette smoking, and hypertension-all conditions involving oxidative stress, lipid peroxidation, and inflammation. To test the role of the lipid peroxidation- and inflammation-derived aldehyde, acrolein, in human vasospasm, we developed an ex vivo model using human coronary artery bypass graft (CABG) blood vessels and a demonstrated acrolein precursor, allylamine. Allylamine induces hypercontraction in isolated rat coronary artery in a semicarbazide-sensitive amine oxidase activity (SSAO) dependent manner. Isolated human CABG blood vessels (internal mammary artery, radial artery, saphenous vein) were used to determine: (1) vessel responses and sensitivity to acrolein, allylamine, and H(2)O(2) exposure (1 microM-1 mM), (2) SSAO dependence of allylamine-induced effects using SSAO inhibitors (semicarbazide, 1 mM; MDL 72274-E, active isomer; MDL 72274-Z, inactive isomer; 100 microM), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca(2+) to hypercontraction. Acrolein or allylamine but not H(2)O(2), benzylamine, or methylamine stimulated spontaneous and pharmacologically intractable hypercontraction in CABG blood vessels that was similar to clinical vasospasm. Allylamine-induced hypercontraction and blood vessel SSAO activity were abolished by pretreatment with semicarbazide or MDL 72274-E but not by MDL 72274-Z. Allylamine-induced hypercontraction also was significantly attenuated in Ca(2+)-free buffer. In isolated aorta of spontaneously hypertensive rat, allylamine-induced an SSAO-dependent contraction and enhanced norepinephrine sensitivity but not in Sprague-Dawley rat aorta. We conclude that acrolein generation in the blood vessel wall increases human susceptibility to vasospasm, an event that is enhanced in hypertension.
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PMID:Acrolein generation stimulates hypercontraction in isolated human blood vessels. 1709 30

Adipocytes express two types of amine oxidases: the cell surface semicarbazide-sensitive amine oxidase (SSAO) and the mitochondrial monoamine oxidase (MAO). In human abdominal subcutaneous adipose tissue, it has been reported that SSAO substrates stimulate glucose transport and inhibit lipolysis while MAO activity is decreased in obese patients when compared to age-matched controls. However, no information has been reported on visceral WAT. To further investigate the obesity-induced regulations of MAO and SSAO in white adipose tissue (WAT) from different anatomical locations, enzyme activities and mRNA abundance have been determined on tissue biopsies from control and high-fat fed dogs, an obesity model already described to be associated with arterial hypertension and hyperinsulinemia. MAO activity was increased in the enlarged omental WAT of diet-induced obese dogs, but not in their mesenteric WAT, another intra-abdominal fat depot. Subcutaneous WAT did not exhibit any change in MAO activity, as did the richest MAO-containing tissue: liver. Similarly, SSAO was increased in omental WAT of diet-induced obese dogs, but was not modified in other WAT and in aorta. The increase in SSAO activity observed in omental WAT likely results from an increased expression of the AOC3 gene since mRNA abundance and maximal benzylamine oxidation velocity were increased. Finally, plasma SSAO was decreased in obese dogs. Although the observed regulations differ from those found in subcutaneous WAT of obese patients, this canine model shows a tissue- and site-specific regulation of peripheral MAO and SSAO in obesity.
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PMID:Increased monoamine oxidase and semicarbazide-sensitive amine oxidase activities in white adipose tissue of obese dogs fed a high-fat diet. 1721 65

The renalase pathway is a previously unrecognized mechanism for regulating cardiac function and blood pressure. In this pathway, renalase, a novel secreted amine oxidase that is inactive at baseline, is rapidly turned on ( ~ 10 fold increase) by either a modest increase in blood pressure or by brief surges in plasma catecholamines. The active enzyme degrades circulating catecholamines, causing a significant fall in blood pressure. Plasma catecholamines not only activate renalase enzymatic activity but also lead to a 3-4 fold stimulation of renalase secretion. The renalase knockout mouse (KO) is hypertensive and exquisitely sensitive to cardiac ischemia. Abnormalities in the renalase pathway are present in animal models of chronic kidney disease (CKD) and hypertension. Two single-nucleotide polymorphisms (SNPs) in the renalase gene were found to be associated with essential hypertension in man. Blood renalase levels are inversely correlated with glomerular filtration rate (GFR) and are markedly reduced in patients with end-stage kidney disease (ESRD). We hypothesize that renalase is secreted into blood by the kidney (although also expressed in heart, skeletal muscle, and small intestine) and plays a key role in regulating blood pressure and cardiovascular function, and that abnormalities in the renalase pathway contribute to the heightened cardiovascular risks observed in patients with CKD.
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PMID:Regulation of blood pressure and cardiovascular function by renalase. 1947 22

These investigations are part of an attempt to study and interpret the intermediary metabolism of the kidneys in experimental renal hypertension. Hypertension was produced in dogs by the clamping procedure of Goldblatt and associates or by the silk perinephritis method of Page. Enzymatic studies were made by means of Warburg's manometric method. Cytochrome c was in addition determined spectrophotometrically. Tissue slices, homogenized tissue, and tissue extracts were used. A study of the cytochrome c concentration and the activities of the cytochrome oxidase and succinic dehydrogenase systems of kidneys from normal dogs and dogs with experimental renal hypertension was made. It was found that the cytochrome c concentration and the activities of the cytochrome oxidase and succinic dehydrogenase systems were markedly lower in the kidney slices and in the tissue suspensions from hypertensive dogs. Tissue suspensions and extracts of kidneys from hypertensive dogs showed an inhibitory effect on the activity of the cytochrome oxidase and succinic dehydrogenase, and the amine oxidase systems. Renin preparations also showed a marked inhibitory effect on the activities of cytochrome oxidase, succinic dehydrogenase, l-amino acid oxidase, and amine oxidase systems. A significant increase was found in the kidney of dogs whose other kidney had been removed or subjected to Goldblatt's or Page's technique in the activities of the cytochrome-cytochrome oxidase system, the succinic dehydrogenase system, and in the concentration of nucleotide-bound phosphorus, of flavin-adenine dinucleotide, and of the nicotinamide-adenine dinucleotides (coenzymes I and II). From the results of these studies it can be concluded that an increase in the concentration and activity of the respiratory enzymes precedes hypertrophy of the kidney. This can be explained by the assumption that an increase in the activity of the respiratory biocatalysts acts as a stimulus for cell growth and multiplication.
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PMID:THE METABOLISM OF THE KIDNEY IN EXPERIMENTAL RENAL HYPERTENSION : II. THE CONCENTRATION OF CYTOCHROME C AND THE ACTIVITIES OF THE CYTOCHROME OXIDASE AND OF THE SUCCINIC DEHYDROGENASE SYSTEMS IN THE KIDNEY OF DOGS WITH EXPERIMENTAL RENAL HYPERTENSION. THE INHIBITORY EFFECT OF RENIN AND OF KIDNEY TISSUE PREPARATIONS FROM HYPERTENSIVE DOGS ON THE RESPIRATORY ENZYMES. 1987 97

Renalase is an amine oxidase expressed in kidney, heart, liver, and brain that metabolizes catecholamines. Tissue and plasma levels are decreased in models of hypertension and chronic kidney disease. Its expression is modulated by salt intake, and urinary renalase may regulate catecholamines levels and effect renal sodium and phosphate transport. The renalase knockout mouse is hypertensive in the absence of significant changes in renal function. Sympathetic tone is increased as evidenced by elevated plasma and urine catecholamines. Studies in humans with resistant hypertension indicate that plasma renalase levels are inversely associated with systolic blood pressure. Additionally, a functional mutation in renalase (Glu37Asp), known to be associated with essential hypertension, also predicts more severe cardiac hypertrophy and dysfunction. Lastly, a single dose of recombinant renalase administered subcutaneously to rats with chronic kidney disease or to Spontaneously Hypertensive Stroke Prone rats significantly decreases blood pressure for more than 24 h. Available data suggest that renalase deficiency is associated with increased sympathetic tone and resistant hypertension, and recombinant renalase is a potent antihypertensive agent that may provide a valuable option for treating hypertension in chronic kidney disease.
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PMID:Novel insights into the physiology of renalase and its role in hypertension and heart disease. 2142 26

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