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 effects of oral contraceptives (OCs) on drug therapy are related mainly to the inhibition of microsomal oxidation as well as the induction of enzymes involved in conjugation reactions. Since many drugs share these catabolic pathways, their pharmacodynamics will be affected by OCs. Notable interactions include an increased bioavailability of analgesics, tranquilizers, and tricyclic antidepressants. OCs increase the risk for hypertension, and pharmacokinetic interactions are to be expected when OCs are administered with antihypertensive drugs. Likewise, OCs affect lipid metabolism and thus modify the effects of atherogenic drugs; however, the different forms of hyperlipidemia show a heterogeneous response to OCs. Another particular concern is that the gestagen components of OCs may cause peripheral insulin resistance and may require dose adaption with antidiabetic treatments. Two common nonprescription drugs, theophylline and caffeine, show decreased clearance rates due to OCs. All share a common oxidation pathway involving cytochrome P-450 and P-448. However, cigarette smoking stimulates these enzymes, and the decreased clearance of theophylline and caffeine is usually not observed in smokers. The reports of effects of OCs and alcohol taken together are mixed, and no clinically relevant conclusions can be drawn. Most vitamin and mineral levels are influenced by OCs, but this is a concern only under conditions of deprived diet, when normal dietary adjustments are impossible. An important caveat of the many documented effects of OCs on the pharmacodynamics of other drugs is that, in most instances, these effects will be counterbalanced with kinetic changes and result in no clinical manifestation. Nevertheless, clinicians must be aware of possible adverse reactions, particularly in predisposed patients.
 ...
PMID:Influence of oral contraceptives on drug therapy. 225 28

Ingestion of licorice or treatment with chemical derivatives of glycyrrhetinic acid (GA), an active principle of licorice, can cause hypertension, sodium retention, and hypokalemia. Although GA has been shown to inhibit 11 beta-hydroxysteroid dehydrogenase, it may not be the only hepatic enzyme affected by this licorice derivative. Therefore, we studied the effects of GA on other major hepatic steroid-metabolizing enzymes from adrenalectomized male rats using aldosterone as the substrate; namely, delta 4-5 alpha- and delta 4-5 beta-reductases and 3 alpha- and 3 beta-hydroxysteroid dehydrogenases (3 alpha- and 3 beta-HSD). From these in vitro studies, we demonstrated that GA does not affect either microsomal 5 alpha-reductase or cytosolic 3 alpha-HSD activity. However, GA is a potent inhibitor of cytosolic 5 beta-reductase; the K(is) and K(ii) were calculated from enzyme kinetic analysis to be 6.79 and 5.41 microM, respectively, using the Cleland equation, indicating that GA is a noncompetitive inhibitor of aldosterone. In addition, GA specifically inhibited microsomal 3 beta-HSD enzyme activity by what appears to be a competitive inhibition mechanism, causing a build-up of the intermediate, 5 alpha-dihydroaldosterone (DHAldo). Thus, this study has indicated that GA has a profound effect on hepatic ring A-reduction of aldosterone. Inhibition of 5 beta-reductase and 3 beta-HSD results in decreased synthesis of both 3 alpha, 5 beta-tetrahydroaldosterone (THAldo) and 3 beta, 5 alpha-THAldo and, hence, accumulation of aldosterone and 5 alpha-DHAldo, both potent mineralocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effects of the licorice derivative, glycyrrhetinic acid, on hepatic 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and 5 alpha- and 5 beta-reductase pathways of metabolism of aldosterone in male rats. 232 27

Differences in [3H]nitrendipine binding sites in brain regions and subcellular fractions from cortex have been investigated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. At 4 weeks of age, [3H]nitrendipine receptor binding (Bmax) was increased in the hypothalamus and striatum of SHR but not WKY rats, whereas no changes were found in the cortex, cerebellum, or brain stem. At 12 weeks of age, [3H]nitrendipine binding (Bmax) was still elevated in the hypothalamus of SHR, whereas binding in the striatum was not significantly different. [3H]Nitrendipine binding in SPM-1 membrane from cortex was elevated at 12 weeks of age, whereas no changes were seen in nuclear, mitochondrial microsomal, or SPM-3. These results demonstrate that prior to elevated blood pressure, [3H]nitrendipine receptor binding is increased in discrete brain regions and membrane fractions and suggest that "L" type calcium channels may be under genetic control and be involved in development of hypertension.
 ...
PMID:Regional and subcellular distribution of [3H]nitrendipine binding sites in SHR and WKY rats. 246 84

We studied in vivo and in vitro steroidogenesis in six phenotypic female children with 17-hydroxylase deficiency. The diagnosis was suspected as a likely cause of familial low renin hypertension and was confirmed by findings of reduced basal and ACTH-stimulated serum and urinary levels of cortisol and other 17-hydroxysteroids, together with hypergonadotropic hypogonadism in both 46,XY and 46,XX patients, and abnormally increased secretion of 17-desoxysteroids, such as progesterone, 11-deoxycorticosterone, and corticosterone. ACTH stimulation testing demonstrated a lesser degree of 17-hydroxylase deficiency in the obligate heterozygous parents; one father had increased basal serum 17-hydroxyprogesterone values, unresponsive to ACTH, suggesting partial Leydig cell 17,20-desmolase deficiency. In vitro kinetic analysis of testicular microsomal enzymes in the affected 46,XY male pseudohermaphrodites confirmed that both 17-hydroxylase and 17,20-desmolase activities were less than 2% of those in age-matched normal subjects. However, in spite of this virtual absence of both enzymatic activities of cytochrome P450c17, Northern blot analysis demonstrated abundant amounts of RNA in these tests that hybridized to a cDNA specific for this P450 enzyme. Moreover, immunoblot analysis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis-resolved testicular microsomes showed an apparently normal content of an immunoreactive protein with a mol wt similar to that of authentic P450c17. These results suggest that these patients have a point mutation in the gene for P450c17; the mutant gene is transcribed, but gives rise to a protein defective in normal 17-hydroxylase and 17,20-desmolase activities.
 ...
PMID:Combined 17-hydroxylase and 17,20-desmolase deficiencies: evidence for synthesis of a defective cytochrome P450c17. 249 25

alpha-Adrenergic receptor subtypes were investigated using [3H]prazosin, an alpha 1 selective antagonist, and the alpha 2 selective antagonist [3H]rauwolscine in a smooth muscle plasma membrane enriched microsomal fraction prepared from rabbit intrarenal arterial vasculature. Both radioligands displayed single components on Scatchard analysis. The specific binding of [3H]prazosin was of high affinity (0.54 +/- 0.04 nM) with a maximum binding capacity (Bmax) of 212 +/- 15 fmol/mg protein. The maximum number of [3H]rauwolscine binding sites was 64 +/- 4 fmol/mg of protein with a dissociation constant (Kd) of 5.60 +2- 0.27 nM. Binding of both radioligands was rapid, saturable, and specific. alpha 1- and alpha 2-adrenergic receptors in the intrarenal arterial membrane preparation were also characterized at 2-, 4-6-, and 10-12-week intervals during the course of development and maintenance of chronic two-kidney, one clip (2K1C) Goldblatt hypertension and in age-matched sham-operated normotensive control rabbits. The alpha 1-adrenergic receptor affinity for [3H]prazosin binding in hypertensive rabbits was significantly increased in the stenotic, but not contralateral, kidney at 2 weeks; however, at 6 weeks the receptor affinity of both kidneys was significantly increased compared with those of the normotensive control group. No difference in alpha 1-adrenergic receptor affinity was seen at 12 weeks, and there were no changes in Bmax at any of the weekly intervals. Neither the Kd, nor Bmax, for [3H]rauwolscine in either kidney showed a significant difference between hypertensive rabbits and normotensive control rabbits. These studies demonstrate the existence in the rabbit intrarenal arterial vasculature of binding sites with alpha 1- and alpha 2-adrenergic receptor specificity.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1989 Jun
PMID:Characterization of intrarenal arterial adrenergic receptors in renovascular hypertension. 254 25

Vascular (Na+,K+)-pump activity (ouabain-sensitive 86Rb+ uptake) and myocardial (Na+,K+)-ATPase activity are reduced in animals with various forms of low renin, experimental hypertension. On the other hand, vascular (Na+,K+)-pump activity is increased in Dahl salt-sensitive relative to resistant rats (a genetic model of hypertension), regardless of salt intake or blood pressure and it is also increased in Dahl salt-sensitive rats on high salt (8% NaCl) relative to low salt (0.4% NaCl) diets. It has been suggested that this increase in vascular (Na+,K+)-pump activity may be secondary to an increase in the vascular sarcolemmal permeability to Na+ in these salt-sensitive rats. In the present study, (Na+,K+)-ATPase activity of left ventricular microsomal fractions, was increased in Dahl salt-sensitive relative to resistant rats on low salt diets; however, this difference disappeared when these salt-sensitive and resistant rats were placed on high salt diets. In contrast, myocardial (Na+,K+)-ATPase activity was decreased in Dahl salt-sensitive rats on high relative to low salt diets. Evidence that this decrease in (Na+,K+)-ATPase activity is not secondary to myocardial hypertrophy in the hypertensive salt-sensitive rats, and mechanisms by which decreased cardiovascular (Na+,K+)-pump activity, increased sarcolemmal permeability or both, might contribute to elevated blood pressure, are discussed.
 ...
PMID:Myocardial (Na+,K+)-ATPase activity in Dahl salt-sensitive and resistant rats. 298 28

Material extracted and partially purified from plasma of the Sabra hypertension prone rats was found to be capable of 1) inhibiting the binding of 3H-ouabain to rat brain synaptosomes, 2) inhibiting the activity of rat brain microsomal Na, K activated adenosine triphosphatase, and 3) increasing the contractile force of rat heart muscle. The results demonstrate the presence of a ouabainlike compound in the plasma of these rats. The plasma concentration of this compound in Sabra hypertension prone rats was 698 +/- 199 nmol/ml in ouabain equivalents (SEM; n = 11) versus 2543 +/- 1140 nmol/ml (n = 9) in the Sabra normotensive strain. The presence of ouabainlike compound in the plasma is consistent with the hypothesis that this compound functions as a hormone that regulates Na, K activated adenosine triphosphatase activity and the physiological processes in which this enzyme is involved.
Hypertension
PMID:Demonstration of a ouabainlike plasma compound in hypertension prone and hypertension resistant rats. 299 63

Inhibition of cardiovascular Na,K-pump activity has been shown to promote an increase in the contractile activity of myocardial and vascular smooth muscle and a consequent rise in blood pressure (BP). It has also been shown that vascular Na,K-pump activity and myocardial Na+K+ATPase activity [the energy source for active sodium (Na) and potassium (K) transport] are decreased in rats with various forms of low renin hypertension including rats with reduced renal mass-saline (RRM-saline) hypertension. In the present study, left ventricular Na+K+ATPase activity from rats with RRM-saline hypertension was found to be decreased in membranes prepared by two independent methods: deoxycholate, sodium iodide (Nal)-treated microsomal fractions (method 1) and membranes prepared by the hypotonic, lithium bromide (LiBr) method (method 2). Relative to RRM normotensive control rats which drank distilled water, myocardial Na+K+ATPase activity from RRM-saline drinking rats was decreased by 18.2% in membranes prepared by method 1 and 33.6% in membranes prepared by method 2. The apparent affinities of Na+K+ATPase for K and for ouabain were unaltered relative to controls in membranes prepared from these hypertensive rats by method 1, and the sialic acid content and 5'-nucleotidase activity (two putative sarcolemmal markers) were unaltered in membranes from the hypertensive rats, prepared by methods 1 and 2 respectively. The Mg2+ATPase activity of membranes prepared by method 1 was increased in the RRM-saline hypertensive rats but because it was not increased in membranes prepared by method 2 the former observation does not appear to be of any pathophysiological importance. In other experiments, hypertension was reversed in RRM-saline hypertensive rats by restricting their salt intake (substitution of distilled water for drinking).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Decreased myocardial Na+K+ATPase activity in rats with reduced renal mass-saline hypertension. 300 89

Myocardial ventricular Na, K-ATPase activity of normotensive rats was compared with that of healthy rats with chronic benign one-kidney, one-clip hypertension. The yield of protein (mg/g wet wt left plus right ventricles) in microsomal and sarcolemmal membrane fractions was the same for both normotensive and hypertensive rat ventricles. However, the yield of protein (mg/ventricle) was 26% greater in the hypertensive relative to the normotensive animals, consistent with the presence of hypertrophy, as also indicated by an increase in the ratio of ventricular to body weight and a shift in the isomyosin composition. Na, K-ATPase activity, sodium-dependent phosphorylation and ouabain binding were significantly (P less than 0.05) decreased (by 20%, 40%, and 45%, respectively) in the hypertensive rat ventricles when the data were expressed in units/g tissue wet weight. However, when expressed in units per ventricle, values in normotensive and hypertensive animals were similar. The molecular activity or turnover number of ventricular (and also renal) Na, K-ATPase activity was the same in both groups of animals. These results suggest that the decrease in myocardial specific Na, K-ATPase activity in the rat made hypertensive by removing one kidney and constricting the renal artery of the other kidney is related to the presence of cardiac hypertrophy.
 ...
PMID:Myocardial Na, K-ATPase in one-kidney, one-clip hypertensive rats. 302 43

Treatment of rats with methylandrostenediol (MAD), an anabolic androgen, caused a profound reduction (65%) in the level of cytochrome P-450 11 beta in rat adrenocortical mitochondria as measured by immunoblots using a specific antibody. The decreases in mitochondrial cytochrome P-450scc (15%) and adrenodoxin (20%) were much less than that observed for cytochrome P-45011 beta. A 35% decrease in adrenal microsomal cytochrome P-450 21 and NADPH-cytochrome P-450 reductase levels was brought about by the treatment with MAD. The data establish that the preferential decrease in adrenal steroid 11 beta-hydroxylase activity associated with androgen treatment results from a decrease in cytochrome P-450 11 beta. This is consistent with the role of 11-deoxycorticosterone in the pathogenesis of androgen-induced hypertension in rats.
 ...
PMID:Levels of adrenodoxin, NADPH-cytochrome P-450 reductase and cytochromes P-45011 beta, P-45021, P-450scc, in adrenal zona fasciculata-reticularis tissue from androgen-treated rats. 312 24


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