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

The changes in the content of pyridine nucleotide coenzymes (NAD+ and NADH) in several models of experimentally induced hypertension, differing in mechanism (genetic spontaneous hypertension, renal one kidney Goldblatt hypertension, Adrenal-regeneration hypertension after INGLE-HIGGINS and Skelton, and NaC1 hypertension) were studied. An obvious difference between the changes in NAD+ and NADH in the various models of hypertension, was established: Thus in NaC1 hypertension a high level of the coenzymes in the kidneys and in the vessel wall was found, while the liver coenzyme content was in normal ranges. In ARH the coenzyme level was elevated not only in the kidneys and in the vessel wall, but in the liver as well. Treatment with hypotensive antilipolytic prostaglandin E1 decreased the coenzymes in ARH to normal values. Renal hypertension was characterized by a low content of oxidized NAD, an increased NADH, and a decreased NAD+/NADH ratio in the kidneys and the liver, while in the vessel wall the coenzyme level was moderately increased. The coenzyme changes in the kidneys of SHR were similar to those in renal hypertensive rats. However coenzyme level in the vessel wall of SHR was lower than in all the other forms of hypertension.
 ...
PMID:Coenzyme alterations in rats with experimental hypertension. 18 74

The effects of oxygen inhalation (FiO2 = 0.4-0.5) and/or induced hypertension (delta MBP = around 20%) on the cortical oxygen tension (CoPO2) and the cortical oxidative metabolism (NADH/NAD redox state) in acute focal ischaemia were studied in 44 rabbits. CoPO2 was recorded by a polarographical method and NADH/NAD redox state was measured with a compensated fluorometer/reflectometer. The acute focal ischaemia was induced by the occlusion of the middle cerebral artery. With oxygen inhalation, CoPO2 improved 24.8 +/- 23.2% (mean +/- SD) in ischaemic areas where CoPO2 decreased to less than 40% of control. The oxygen inhalation also partially improved NADH levels in ischaemia by 1.5 +/- 1.6% in 8 rabbits, where NADH elevated 17.6 +/- 12.1% from the normal stage. CoPO2 and NADH redox level in ischaemia were also improved by induced hypertension. delta CoPO2/delta MBP were 1.29 +/- 1.53%/mmHg in the severely ischaemic area (less than 20% of control), 1.52 +/- 0.93 in the moderately ischaemic area (20-40% of control), and 1.03 +/- 0.62 in the mildly ischaemic area (greater than 40% of control), respectively. delta NADH/delta MBP were statistically greater in the ischaemic area than in the normal cortex (p less than 0.005). It is concluded that mild hyperoxia and induced hypertension both of which are easily employed not only can improve cortical oxygen tension but also partially restore the oxidative metabolism in acute focal ischaemia.
 ...
PMID:The effects of mild hyperoxia and/or hypertension on oxygen availability and oxidative metabolism in acute focal ischaemia. 257 48

Concentrations of prostaglandins E2 and I2 may be decreased in preeclamptic and eclamptic pregnancies. Because these prostaglandins produce vasodilation and inhibit platelet aggregation it has been suggested that a reduction in their biosynthesis might play an important role in the pathogenesis of the hypertension and coagulation abnormalities associated with preeclampsia. Placental tissue is an extremely rich source of several enzymes that catalyze the catabolism of prostaglandins. The present study was initiated to determine whether one of these catabolic enzymes might be increased in preeclamptic/eclamptic pregnancies. The activities of the NAD- and the NADP-linked 15-hydroxyprostaglandin dehydrogenases were measured in 16 preeclamptics (mean diastolic pressure, 108 +/- 13 mmHg) and compared with 16 normotensive controls matched for age (20.8 +/- 5.43 vs. 20.6 +/- 5.16) and gestational week of delivery (34.6 +/- 5.40 vs. 35.0 +/- 5.06). These results indicate that the activity of the placental NAD-linked 15-hydroxyprostaglandin dehydrogenase is elevated in preeclampsia (40.1 +/- 31.3 vs. 14.9 +/- 8.30 mU/g tissue, P less than 0.01). If this increase were also expressed in vivo, its effect on prostaglandin metabolism could be mistaken for impaired prostacyclin biosynthesis unless both the 6-keto- and 6,15-diketo-metabolites of prostacyclin were measured.
 ...
PMID:In vitro activity of nicotinamide adenine dinucleotide- and nicotinamide adenine dinucleotide phosphate-linked 15-hydroxyprostaglandin dehydrogenases in placentas from normotensive and preeclamptic/eclamptic pregnancies. 330 60

Parallel stereo- and cytospectrophotometric examinations of human myocardial capillaries, 20-60 min after biological death were carried out. The activity of alkaline phosphatase, adenosine triphosphatase, lactate dehydrogenase and NAD-diaphorase in the capillary wall in relation to the sex and age in cardiovascular pathology, renal diseases and leukemias were studied. The permeability and level of energy supply of transendothelial transport were found to depend on the kind of the main pathological process and type of death. According to the parameters under study, the functional state of the capillary network of the myocardium in atherosclerosis with or without its combination with hypertension and also in secondary renal hypertension is described.
 ...
PMID:[Stereological characteristics and enzymatic activity of myocardial capillaries in different variants of pathology and death (data from immediate autopsies)]. 686 Jan 68

The effects of stepwise arterial hypotension (MABP: 80, 60, 40 mm Hg) and moderate arterial hypo- and hypertension (MABP: 80, 150-160 mm Hg) on cerebrocortical vascular volume and NAD/NADH redox state were studied in anaesthetized cats. The vascular volume and NADH fluorescence measurements were performed on closed skull preparations using a microscope fluororeflectometer. To determine the possible role of adrenergic alpha-receptors in the autoregulatory adjustment of cerebrocortical vascular volume, some of the animals were pretreated with intra-arterially infused phenoxybenzamine (1 mg/kg). It was found that longlasting stepwise arterial hypotension leads to a gradual increase in cerebrocortical vascular volume and NADH fluorescence. Though the cerebrocortical arteries dilatated considerably at 80 mm Hg, sustained for 30 min, the NAD/NADH redox state failed to be reoxidized but was shifted to a more reduced state. This finding suggests that some factor other than tissue hypoxia is responsible for the dilatation of cerebrocortical vessels during moderate arterial hypotension. When the arterial blood pressure was restored following stepwise arterial hypotension, the cerebrocortical vascular volume did not decrease and the NAD/NADH redox state remained reduced, showing that the autoregulatory capability of the vessels was lost and the tissue metabolism was irreversibly altered. During a 5-min duration of moderate arterial hypo- and hypertension, biphasic changes were obtained in cerebrocortical vascular volume while the NAD/NADH redox state was shifted to a more reduced and oxidized state. Since the dilatation and the constriction of the cerebrocortical vessels during arterial hypo- and hypertension lagged by 40-80 s behind the redox state alterations, it is suggested that the myogenic mechanism has a minor role in CBF autoregulation. Phenoxybenzamine (PBZ) dilatated the cerebrocortical vessels, indicating the existence of an active alpha-receptor-mediated vasoconstrictory tone. Since the extent of autoregulatory vascular volume changes was not affected by PBZ pretreatment, the involvement of adrenergic alpha-receptors in the autoregulation of CBF can be excluded, at least for cats.
 ...
PMID:Effect of acute arterial hypo- and hypertension on cerebrocortical NAD/NADH redox state and vascular volume. 707 33

11 beta-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the conversion of cortisol to cortisone and corticosterone to 11-dehydrocorticosterone. This activity may be required to confer normal ligand specificity upon the mineralocorticoid receptor. Although an isozyme of 11-HSD was previously isolated from rat liver, a different isozyme is apparently expressed in mineralocorticoid target tissues. We isolated a sheep kidney cDNA clone encoding this isozyme by expression screening using Xenopus oocytes. The cDNA is 1.8 kb in length and encodes a protein of 427 amino acid residues with a predicted M(r) of 46,700. When expressed in oocytes, this enzyme functions as an NAD(+)-dependent 11 beta-hydrogenase with very high affinity for steroids, but it has no detectable reductase activity. It is 37% identical in amino acid sequence to an NAD(+)-dependent isozyme of 17 beta-hydroxysteroid dehydrogenase, but only 20% identical to the NADP(+)-dependent liver isozyme of 11-HSD. It is expressed at high levels in the kidney and adrenal and at lower levels in the colon. The corresponding gene is present in a single copy in the sheep genome. In humans, this gene is a candidate locus for the syndrome of apparent mineralocorticoid excess, a form of hypertension postulated to result from 11-HSD deficiency in mineralocorticoid target tissues.
 ...
PMID:Cloning of cDNA encoding an NAD(+)-dependent isoform of 11 beta-hydroxysteroid dehydrogenase in sheep kidney. 758 2

Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) have been described which catalyze the interconversion of cortisol (F) to cortisone (E). 11 beta HSD activity has previously been reported in placenta and fetal membranes, where its role may be to protect the developing fetus from glucocorticoid excess. Furthermore, in the rat, an association between placental 11 beta HSD activity and the subsequent development of hypertension in the offspring has been reported. We have characterized the isoforms of 11 beta HSD in human fetal membranes and dissected placental tissue at term and investigated the relationship between placental 11 beta HSD activity and fetal and placental weights. 11 beta HSD activity studies in the presence of 0.1 mumol/L F and NAD (indicative of type 2 isoform activity) revealed high levels of activity in trophoblast dissected free of vessels (561 +/- 87 pmol E/h.mg protein; n = 4) > undissected placenta > cotyledenous vessels dissected away from trophoblast > placental and reflected amnion. In contrast, in the presence of 2.5 mumol/L F and NADP (indicative of type 1 isoform activity), only decidua and chorion demonstrated significant levels of 11 beta HSD activity. Type 1 11 beta HSD activity in chorion was probably due to decidual contamination, in that it was absent in decidua-free fused chorion obtained from a twin pregnancy. In keeping with these data, type 1 11 beta HSD messenger ribonucleic acid (1.5 kilobases) was detected in decidua, but in no other tissue, and high levels of type 2 11 beta HSD messenger ribonucleic acid (1.9 kilobases) were found in undissected placenta and trophoblast. In 27 term placentas, 11 beta HSD activity varied from 194-448 pmol E/h.mg protein. There was a weak, but significant, positive correlation between term placental 11 beta HSD activity and fetal weight (r = 0.408; P = 0.034), but no correlation with placental weight. Thus, in man, the reported association of a small fetus and a large placenta predisposing to adult hypertension cannot be explained on the basis of defective 11 beta HSD activity. However, the placenta offers an immense reservoir for F clearance (1.73-7.95 mumol/min.placenta) and may be a principal factor driving fetal ACTH secretion and, hence, fetal adrenal steroidogenesis.
 ...
PMID:Type 2 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal adrenal steroidogenesis. 788 47

11 beta-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the conversion of cortisol to cortisone and corticosterone to 11-dehydrocorticosterone. This activity may be required to confer normal ligand specificity upon the mineralocorticoid receptor. Although an isozyme of 11-HSD was previously isolated from rat liver, a different isozyme is apparently expressed in mineralocorticoid target tissues. We isolated a sheep kidney cDNA clone encoding this isozyme by expression screening using Xenopus oocytes. The cDNA is 1.8 kilobase pairs in length and encodes a protein of 427 amino acid residues with a predicted M(r) of 46,700. When expressed in oocytes, this enzyme functions as an NAD(+)-dependent 11 beta-dehydrogenase with very high affinity for steroids, but it has no detectable reductase activity. It is 37% identical in amino acid sequence to an NAD(+)-dependent isozyme of 17 beta-hydroxysteroid dehydrogenase but only 20% identical to the NADP(+)-dependent liver isozyme of 11-HSD. It is expressed at high levels in the kidney and adrenal and at lower levels in the colon. The corresponding gene is present in a single copy in the sheep genome. In humans, this gene is a candidate locus for the syndrome of apparent mineralocorticoid excess, a form of hypertension postulated to result from 11-HSD deficiency in mineralocorticoid target tissues.
 ...
PMID:NAD(+)-dependent isoform of 11 beta-hydroxysteroid dehydrogenase. Cloning and characterization of cDNA from sheep kidney. 792 4

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates the access of corticosteroids to their receptors and is important in blood pressure control. The excretion of renal 11 beta-HSD (ie, NAD(+)-dependent isoform) is thought to protect renal mineralocorticoid receptors from cortisol. To examine whether endogenous renal 11 beta-HSD inhibitory factor(s) may be involved in the pathophysiology of hypertension, we studied the urinary excretion of such inhibitors in 30 patients with low-renin essential hypertension and 20 normotensive control subjects. The effect of sodium restriction on the urinary excretion of the inhibitors wa also evaluated in six normotensive control subjects. Urine was extracted with Sep-Pak cartridges and high-performance liquid chromatography. Endogenous renal 11 beta-HSD inhibitors were measured by the inhibition of 11 beta-HSD bioactivity in microsomes from the human kidney. The urinary excretion of the inhibitors was significantly increased in patients with low-renin essential hypertension (1280 +/- 88 nmol/d, mean +/- SEM) compared with normotensive control subjects (704 +/- 56 nmol/d) (P < .05). Ratios of urinary tetrahydrocortisol+allo-tetrahydrocortisol to tetrahydrocortisone did not differ significantly. Sodium restriction reduced the urinary excretion of the endogenous renal 11 beta-HSD inhibitors but did not affect the ratio of urinary tetrahydrocortisol+allo-tetrahydrocortisol to tetrahydrocortisone. Endogenous renal 11 beta-HSD inhibitory factors may contribute to the pathogenesis of low-renin essential hypertension by modulating the activity of 11 beta-HSD. Sodium intake may directly or indirectly regulate the inhibitory factors.
Hypertension 1996 Feb
PMID:Endogenous renal 11 beta-hydroxysteroid dehydrogenase inhibitory factors in patients with low-renin essential hypertension. 856 41

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates glucocorticoid interactions with mineralocorticoid and glucocorticoid receptors in vivo, by converting 11 beta-hydroxyglucocorticoids to their inactive 11-ketone derivatives. Defective 11 beta-oxidation of glucocorticoids has been associated with hypertension. The objective of this study was to investigate whether 11 beta-HSD contributes to the occurrence of hypertension in spontaneously hypertensive rats (SHRs). The liver and kidney microsomal oxidations of corticosterone (the physiological glucocorticoid in rats) in organs from juvenile (3 weeks old) and adult (3 months old) SHR and Wistar-Kyoto (WKY) rats, with NAD and NADP, show no differences between rat strains. For cortisol, with NADP, adult SHRs show (1.3-3 times; P < 0.05) lower kidney microsomal oxidation rates. The liver microsomal reduction of cortisone shows remarkable interstrain differences; with NADH, reduction is conducted only by adult WKY rats, whereas with NADPH, juvenile animals show similar reduction rates, but at adulthood, only WKYs reduce cortisone. Using Western blot analysis with antibodies against 11 beta-HSD1, positive signals are obtained only for liver microsomes, appearing somewhat lower in SHRs for juvenile but not adult animals. Urinary corticosterone/11-dehydrocorticosterone ratios (measured in adult animals) are not different between rat strains, but are elevated after administration of corticosterone in both strains (although significant only in SHRs). The data provide no indications for exaggerated stimulation of renal corticosteroid receptors, due to modified 11 beta-HSD, in SHRs. However, the experiments suggest the existence of multiple 11 beta-HSDs, in addition to 11 beta-HSD1 and 11 beta-HSD2, some of which may be modified in SHR, but the nature and physiological role of these 11 beta-HSDs is unclear.
 ...
PMID:Comparison of 11 beta-hydroxysteroid dehydrogenase in spontaneously hypertensive and Wistar-Kyoto rats. 858 2


1 2 3 4 5 6 7 8 9 10 Next >>