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)

Renal prostaglandins have been implicated in the regulation of blood pressure. We have therefore compared prostaglandin metabolism in the kidneys of spontaneously hypertensive rats (SHR's) of the Aoki-Okamoto strain and normotensive Wistar-Kyoto (WKY) controls. The microsomal fraction of the renal medulla contained most of the prostaglandin synthetase activity in both groups; SHR's had significantly higher enzymatic activity than their normotensive controls at age 10 wk and thereafter; furthermore, synthetase activity in SHR's increased with age. Two forms of 15-hydroxyprostaglandin dehydrogenases were demonstrated: an NAD+-dependent form which was localized mainly in the cortex and an NADP+-dependent form, higher in the medulla. The activities of these enzymes were lower in the hypertensive animals at all ages studied; this depression was more pronounced for the NAD+-dependent dehydrogenase. The results indicate that, in hypertension, renal prostaglandin metabolism is altered so that enhanced synthesis is accompanied by decreased degradation rate.
 ...
PMID:Prostaglandin metabolism in the kidneys of spontaneously hypertensive rats. 1 24

The norepinephrine (NE) concentration of cardiac ventricles was determined by radioenzymatic assay in normotensive Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone rats (SPR) at 3-6, 14-19, and over 31 weeks of age. There was no difference between strains prior to hypertension, but a progressive decrease in cardiac NE concentration occurred in SHR and particularly in SPR relative to WKY after hypertension was established. This decrease was not due to cardiac hypertrophy. The cardiac neuronal NE storage capacity in rats over 31 weeks of age was analyzed by determining the maximum concentration of NE obtained in a cardiac microsomal fraction, after saturation in vivo with exogenous NE. The results indicated that, after a long period of hypertension, there was a reduction in cardiac NE storage capacity resulting from a loss either of sympathetic nerve endings or of storage vesicles. Moreover, in addition to this reduction in the total size of the cardiac NE store, there was an independent reduction in the degree of filling of this store in both SHR and SPR. This could reflect an increased turnover of cardiac NE in chronically hypertensive SHR and SPR.
 ...
PMID:Changes in cardiac norepinephrine in spontaneously hypertensive and stroke-prone rats. 9 73

The precise role of the kidney in spontaneous experimental hypertension is unknown. We have analyzed the rates of renal prostaglandin synthesis by utilizing a spontaneously hypertensive rat model. The synthetic rate of prostaglandin E2, prostaglandin F2alpha, and prostaglandin A2-like products was measured in vitro with renal microsomes. In the rabbit and rat there is a steep gradient of microsomal prostaglandin synthetase from papilla to cortex with highest activities in the papilla. Comparison of the activity of prostaglandin synthetase in medullary microsomes form normotensive and hypertensive rats showed accelerated synthesis in the spontaneously hypertensive rat. These differences appeared after several months of age, were statistically significant from 3 mo of age and, on the average, represented at least a twofold increase of in vitro activity. All classes of prostaglandins were involved with increased synthesis of prostaglandin E2, prostaglandin F2alpha and prostaglandin A2-like material. These data reenforce and extend previous work showing alterations of granularity and presumably prostaglandin synthesis in renal medullary intersitital cells in various experimental hypertensions. We also measured renal tissue content of prostaglandin E and prostaglandin A-prostaglandin B by radioimmunoassay. Swift and careful handling of the tissue was necessary to avoid extensive postmortem synthesis of prostaglandins. In rapidly-frozen medullary tissue only prostaglandin E was detectable in concentrations ranging from 10 to 200 pg/mg tissue. No significant differences were found in the medullary content of prostaglandin E in the control and hypertensive rats despite the increased rates of enzymatic synthesis. We conclude that renal prostaglandin synthesis is increased in renal medullary microsomes obtained from spontaneously hypertensive rat. This apparently occurs in response to the progressive development of hypertension since young animals did not show an increase Renal tissue prostaglandin E content did not increase and therefore appears to be a poor index of enhanced prostaglandin synthesis.
 ...
PMID:Renal prostaglandin synthesis in the spontaneously hypertensive rat. 82 78

1. The metabolic role of arterial angiotensin I-forming enzyme (i.e. renin activity) was studied in total homogenates and in subcellular fractions of the aorta of normotensive and hypertensive rats. 2. Angiotensin I-forming enzyme was measured in (a) uninephrectomized rats rendered hypertensive with D-aldosterone and sodium chloride (10 g/l drinking solution, (b) rats treated in the same manner but with the addition of spironolactone, and (c) control rats. 3. Hypertension developed in aldosterone-treated rats within 3-6 weeks and was associated with decreased plasma and renal renin values. Total aortic renin activity was up to sixfold higher in the hypertensive animals than in control animals and there was an increased ratio of supernatant to microsomal renin activity in the aorta. 4. In spironolactone-treated rats blood pressure and total aortic renin concentrations were comparable with those in the control rats. 5. The results support the hypothesis that renin generated at local vascular sites, which is independent of circulating renin levels, contributes to regulation of blood pressure.
 ...
PMID:Effects of aldosterone and spironolactone on arterial renin in rats. 107 85

We have previously reported that myocardial microsomal Na+,K(+)-ATPase activity, arterial wall ouabain-sensitive 86Rb uptake, and arterial smooth muscle cell membrane potentials are decreased and plasma Na(+)-K+ pump inhibitory activity is increased in rats during the fifth week of one-kidney, one-clip hypertension. We here report measurements of these four parameters and blood pressure following unclipping. A new series of rats with one-kidney, one-clip hypertension was prepared. Each animal was paired with a one-kidney, sham-clipped (nonconstricting clip) control rat. After 5 weeks, the clips were removed. In the hypertensive animals arterial pressure promptly (within 3 h) returned to normal and remained at the level for 7 observation days. On the third day following unclipping, all four parameters were not significantly different from those in the paired control animals. On the seventh day following unclipping, three of the four parameters were not significantly different from those in the paired control animals and arterial ouabain sensitive 86Rb uptake was slightly increased relative to the value in the control animals. These studies invite further inquiry into the possible role of plasma Na(+)-K+ pump inhibitory activity in the genesis and maintenance of the hypertension in this model.
 ...
PMID:Reversal of one-kidney, one-clip hypertension in rats. Effects on myocardial Na+, K(+)-ATPase, arterial Na(+)-K+ pump, arterial membrane potential, and plasma Na(+)-K+ pump inhibitory activity. 166 Feb 80

Lupus anticoagulant, anticardiolipin, antinuclear, anti-deoxyribonucleic acid, antithyroglobulin, and antithyroid microsomal antibodies were assayed during third-trimester pregnancy (100 normal, 100 with complications). In spite of a normal activated partial thromboplastin time in all instances, lupus anticoagulant was further investigated by three additional procedures: tissue thromboplastin inhibition time, platelet neutralization procedure, and cephalin neutralization test. The prevalence of autoantibodies in pregnancies with hypertension reaches 16% (four with lupus anticoagulant, two with anticardiolipin, and two with antithyroid microsomal antibodies), which is significantly greater than that for idiopathic fetal growth retardation (2%) (one with lupus anticoagulant antibodies) and normal pregnancies (3%) (two with antithyroglobulin and one with autithyroid microsomal antibodies) (p less than 0.01). Autoantibodies were equally distributed between patients with gestational hypertension and those with preeclampsia. When compared with the 42 patients with hypertension and no autoantibodies, the eight patients with autoantibody had a more frequent history of fetal growth retardation (p less than 0.05), but there was no difference in the severity of hypertension, the frequency of obstetric complications, or the outcome of pregnancy. They did not require any specific treatment.
 ...
PMID:The prevalence of autoantibodies during third-trimester pregnancy complicated by hypertension or idiopathic fetal growth retardation. 185 15

The Type I (mineralocorticoid) receptor has identical affinities in vitro for cortisol and aldosterone. It has been suggested that the selective role of aldosterone in regulating sodium homeostasis relies on the microsomal enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD). This enzyme converts cortisol to its inactive metabolite, cortisone, preventing cortisol from binding to the Type I receptor. We have isolated human cDNA clones encoding 11-HSD from a human testis cDNA library by hybridization with a previously isolated rat 11-HSD cDNA clone. The cDNA contains an open reading frame of 876 bases, which predicts a protein of 292 amino acids. The sequence is 77% identical at the amino acid level to rat 11-HSD cDNA. The mRNA is widely expressed, but the level of expression is highest in the liver. Hybridization of the human 11-HSD cDNA to a human-hamster hybrid cell panel localized the single corresponding HSD11 gene to chromosome 1. This gene was isolated from a chromosome 1 specific library using the cDNA as a probe. HSD11 consists of 6 exons and is at least 9 kilobases long. The data developed in this study should be applicable to the study of patients with hypertension due to apparent mineralocorticoid excess, a deficiency in 11-HSD activity.
 ...
PMID:The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization. 188 95

A phenobarbital-inducible rat hepatic microsomal UDP-glucuronosyltransferase (UDPGT) that catalyzes the glucuronidation of 4-hydroxybiphenyl (4-HBP) has been purified to homogeneity. This UDPGT has an apparent subunit molecular weight of 52,500, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 4-HBP UDPGT was shown to catalyze the glucuronidation of 4-HBP, 4-methylumbelliferone, and p-nitrophenol but did not react with testosterone, androsterone, morphine, chloramphenicol, 4-hydroxycoumarin, or 7-methoxycoumarin. The apparent Km of 4-HBP UDPGT for 4-HBP was determined to be 0.26 mM and for UDPGA was 1.0 mM. Upon treatment with endoglycosidase H, the 4-HBP UDPGT underwent about a 2000-dalton decrease in subunit molecular weight, suggesting that this protein is N-glycosylated. Additionally, this protein demonstrated immunoreactivity with antibodies raised in rabbit against rat 17 beta-hydroxysteroid and 3 alpha-hydroxysteroid UDPGTs. This work describes the purification and characterization of a 4-HBP UDPGT from rat liver microsomes and, furthermore, provides evidence that suggests that this UDPGT is different from another UDPGT previously shown to react with 4-HBP and chloramphenicol.
 ...
PMID:Purification and properties of a rat liver phenobarbital-inducible 4-hydroxybiphenyl UDP-glucuronosyltransferase. 190 77

There is little available literature on possible drug interactions involving retinoids despite their widespread use. Unlike some other molecules, the retinoids regardless of their generation do not entail a high risk of interference with other medications. A current study found that concomitant administration of etretinate did not significantly modify the timing or value of the peak serum level of 8 methoxy sporalene. Isotretinoin seems to have an inhibiting effect on certain microsomal hepatic and cutaneous oxydases. An isolated observation has been reported of reduced serum concentration of the antiepileptic Carbamazepine in a patient treated with isotretinoin for severe acne. The report, through unconfirmed, should prompt intensified monitoring of patients receiving antiepileptics and retinoids. Among potential pharmacodynamic interactions, studies with the most evident practical importance have assessed possible interference of orally administered retinoids with the efficacy of oral contraceptives (OCs). 1 study of isotretinoin and OCs concluded on the basis of serum levels of progesterone on the 21st or 22nd cycle day that there was no interference. Another study using the same evaluation criteria concluded that there is no interaction between the aromatic retinoids etretinate or acitretin and OCs. The use of low-dose progestins is however not recommended. A recent study on healthy volunteers demonstrated the absence of influence of acitretin on the efficacy of the antivitamin K agent phenprocoumon. The combination of cyclines with isotretinoin can cause intracranial hypertension and is formally contraindicated. Intracranial hypertension has also been reported with aromatic retinoids, which are not recommended. The combination of lithium and retinoids should also be avoided. Because of the additive effect of undesirable side effects, the combination of retinoids and potentially hepatotoxic molecules especially methotrexate and of isotretinoin and potentially photosensitizing molecules should be avoided.
 ...
PMID:[Retinoids: drug interactions]. 206 36

Cytochrome P450 content and activities are increased in the kidneys of spontaneously hypertensive rats (SHR) as compared with those of normotensive, Wistar-Kyoto (WKY), control rats during the period of rapid elevation of blood pressure. We studied the effect of heme arginate, a potent inducer of heme oxygenase (EC 1.14.99.3), on microsomal cytochrome P450 levels and activities and blood pressure in SHR at 7 wk of age. Administration of heme arginate (15 mg/kg body weight for 4 d) resulted in a marked decrease in blood pressure from 156.3 +/- 4.7 to 129.8 +/- 4.5 mm Hg (P less than 0.001), whereas blood pressure in SHR receiving the vehicle control was not affected. The blood pressure of age-matched WKY was not affected by heme arginate. Heme oxygenase activity increased in both hepatic and renal microsomes of SHR and WKY by two- to four-fold after treatment with heme arginate. Maximal increase of heme oxygenase mRNA occurred 5-7 h after the last injection of heme arginate and returned to control levels after 24 h. The increase in heme oxygenase activity was associated with a parallel decrease in cytochrome P450 content and in the activity of cytochrome P450 omega/omega-1 arachidonate hydroxylases in kidneys of SHR. It is postulated that heme arginate treatment resulted in induction of heme oxygenase which consequently led to a diminution of cytochrome P450, especially the arachidonate omega/omega-1 hydroxylases leading to a marked decrease in 19-hydroxyeicosatetraenoic acid (HETE) and 20-HETE. The effect of heme arginate on blood pressure may be mediated via these biochemical events inasmuch as both 19-HETE and 20-HETE produced by the kidney may promote hypertension by causing vasoconstriction and sodium retention.
 ...
PMID:Effect of heme arginate administration on blood pressure in spontaneously hypertensive rats. 211 25


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