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)

Nonparallel effects of renin inhibitor treatment on plasma renin activity (PRA) and the plasma levels of angiotensins (ANG), as well as on blood pressure, have been observed in subjects with hypertension. This study addresses the possibility that renin inhibitors may show a high degree of plasma protein binding in vivo and that displacement of protein-bound inhibitor during the assay of PRA in vitro may lead to overestimation of renin inhibition. Indeed, with the ultrafiltration technique it was found that 96% of the novel renin inhibitor Ro 42-5892, when added to EDTA plasma, was bound to protein. The angiotensinase inhibitors phenylmethylsulfonyl fluoride (PMSF) and 8-hydroxy-quinoline sulfate (8-OHQ), which are currently used in PRA assays, caused a displacement of protein-bound inhibitor, thereby increasing its free concentration. This displacement was sufficient to explain the reduction in IC 50 of Ro 42-5892, which was seen in the PRA assay when PMSF and 8-OHQ were added to plasma. Such reductions in IC 50 were also seen with the renin inhibitors CGP 29-287, CGP 38-560A, and SR 43-845. When Ro 42-5892 was given, 1 mg/kg intravenously in 10 min, to subjects with hypertension, it appeared that plasma ANG I and II returned to baseline after 6-8 h, whereas PRA measured in the presence of PMSF and 8-OHQ was still suppressed. However, when PRA was measured without these angiotensinase inhibitors, the inhibition of PRA was parallel to the suppression of ANG I and II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nonparallel effects of renin inhibitor treatment on plasma renin activity and angiotensins I and II in hypertensive subjects. An assay-related artifact. 187 15

To explore whether an altered metabolic pathway of dihydroxyphenylalanine (DOPA) may be related to some previously observed dopamine abnormalities in borderline hypertension, we measured basal and DOPA-induced (500 mg orally) changes in blood pressure and pulse rate as well as in three hourly plasma and urine samples. We found that borderline hypertensive patients compared with controls 1) showed a higher baseline urinary excretion of methoxytyramine, a marker of exocytotic dopamine release, with a greater DOPA-induced decrease of systolic blood pressure without reflex tachycardia; 2) had in response to DOPA a blunted plasma DOPA and free dopamine increase but an accentuated plasma dopamine sulfate and urinary DOPAC excretion; and 3) eliminated comparable quantities of dopamine in urine despite a lower rise in the glomerular DOPA load. Furthermore, although DOPA elicited natriuresis in both groups, its effect was greater in borderline hypertensive patients, who lacked the urinary sodium correlation with urinary dopamine excretion seen in control subjects. These data are compatible with increased basal exocytotic dopamine release and accelerated neuronal and renal (extraneuronal) dopamine generation from administered DOPA in borderline hypertension. The DOPA-induced hypernatriuresis exceeding augmented dopamine in borderline hypertensive patients, contrasting with the urinary sodium and dopamine correlation in control subjects, suggests that DOPA induced an additional natriuresis in borderline hypertensive patients by a decrease in renal sympathetic tone because of its central inhibition of sympathetic outflow, which also may account for the absence of reflex tachycardia.
Hypertension 1991 Jun
PMID:Dopaminergic abnormalities in borderline essential hypertensive patients. 190 3

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.
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PMID:Purification and properties of a rat liver phenobarbital-inducible 4-hydroxybiphenyl UDP-glucuronosyltransferase. 190 77

Seizure prophylaxis is standard intrapartum therapy for patients with pregnancy-induced hypertension. Magnesium sulfate is used in the United States in spite of limited literature comparing its efficacy with other anticonvulsants. Fifty patients with pregnancy-induced hypertension were prospectively randomized to receive magnesium sulfate or phenytoin for seizure prophylaxis. Patients were observed for toxicity, side effects, and labor outcomes, and the neonates were evaluated for side effects of the therapy. Three patients were excluded with adverse reactions to medications (one in magnesium sulfate group, two in phenytoin group). No differences were found in patient tolerance, adverse reactions, or neonatal outcomes between groups. Maternal free phenytoin levels were 13.0% +/- 0.4% of total phenytoin (serum albumin, 2.5 to 3.5 gm/dl), significantly higher than in nonpregnant patients. Neither free phenytoin levels nor percentage of total phenytoin that was free correlated significantly with maternal albumin levels. The pharmacokinetics of phenytoin loading in the massively obese pregnant patient may differ and require further evaluation. Phenytoin is a well-tolerated alternative to magnesium sulfate for seizure prophylaxis in the patient with mild pregnancy-induced hypertension.
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PMID:Magnesium sulfate versus phenytoin for seizure prophylaxis in pregnancy-induced hypertension. 195 52

We detected a novel vasoconstrictor in an arginine esterase fraction separated from fractions containing tonin and other esterases that were obtained from a rat submandibular gland extract. When tested on isolated rabbit aorta rings, the substance caused dose-related contractions that were slow in onset, long-lasting, and difficult to reverse by rinsing. The substance acts directly on vascular smooth muscle, since preincubation with plasma or intact endothelium is not required. The fact that the constrictor was destroyed by heat and incubation with pronase suggests that it is a protein. Molecular sieving indicates an estimated molecular weight of 24,000 Da. It has a neutral isoelectric point that is higher than the pI of tonin, from which it can be separated by anion exchange chromatography. A small amount of the vasoconstrictor was obtained by gel filtration and eluted from isoelectric focusing polyacrylamide gels. The purified substance showed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was a potent vasoconstrictor; an estimated concentration of 2.5 nM induced contraction of isolated rabbit aorta rings ranging from 15% to 40% of the maximum contraction obtained by 60 mM KCl. Contraction was completely blocked by 1 mM (p-amidinophenyl)methanesulfonyl fluoride, a serine protease inhibitor. Contractile activity was not affected by hirudin, a thrombin inhibitor, but was completely inhibited by soybean trypsin inhibitor and blunted by aprotinin; thus it may be a trypsin-like serine protease. Purified vasoconstrictor preparation showed hydrolyzing activity on Pro-Phe-Arg-methyl-coumarin amide, a kallikrein substrate. We conclude that a novel vasoconstrictor serine protease is present in the rat submandibular gland.
Hypertension 1991 Jan
PMID:A potent vasoconstrictor in the rat submandibular gland. 198 78

The purpose of this study was to examine the effect of the sulfate ion on blood pressure in DOCA-salt hypertension, which involves increased sympathetic nervous activity. Male Wistar rats were divided into four groups, and received one of the following drinking solutions: distilled water [control], 171 mmol/L sodium chloride [NaCl group], 171 mmol/L sodium chloride plus 12 mmol/L magnesium sulfate [S(+) group], or 171 mmol/L sodium chloride plus 12 mmol/L magnesium chloride [S(-) group]. In the S(+) group, the elevation of systolic blood pressure (SBP; mm Hg) was significantly attenuated (168 +/- 17 v 213 +/- 26, P less than .005) and intraerythrocyte calcium concentration (R-Ca; mumol/L cells) was significantly lower (11.5 +/- 3.0 v 17.4 +/- 6.5, P less than .05) than in the S(-) group. The cardiac norepinephrine content (H-NE; ng/100 g tissue) of the S(+) group was significantly lower than that of the S(-) group. SBP was correlated negatively with H-NE (r = -0.70, P less than .001) and positively with R-Ca (r = 0.45, P less than .005). R-Ca was negatively correlated with H-NE (r = -0.36, P less than .05). These results suggest that the replacement of chloride with sulfate ion suppresses the development of hypertension in DOCA-salt rats at least in part by its inhibitory effect on sympathetic nervous activity through the decreased intracellular calcium concentration.
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PMID:Suppressive effect of sulfate on the development of hypertension in DOCA-salt hypertensive rats. 202 48

Proteoglycan (PG) synthesis in the cardiovascular system of coarctation hypertensive rats was examined by in vivo and in vitro labeling of glycosaminoglycans with 35SO4 in rats made hypertensive for short (4 days) and longer (14 days) durations. With in vivo labeling, only tissues directly exposed to elevated pressure (left ventricle, LV and aorta above the clip, AOR increases) exhibited elevated PG synthesis after 4 days of hypertension. By 14 days, tissues both exposed to (LV and AOR increases) and protected from elevated pressure (right ventricle and kidney) exhibited elevated PG synthetic rates. Slight elevations in the proportion of galactosaminoglycans were observed with a concurrent proportional decrease in heparan sulfate PGs. Using the in vitro labeling procedure, no significant increases in PG synthesis were observed in any tissue at either 4 days or 14 days of hypertension. These data indicate that: 1) coarctation hypertension stimulates PG production that is dependent initially on increased pressure and later, on additional non-pressure related factors, 2) these other factors are responsible for enhanced PG production in tissues not directly exposed to pressure overload, 3) pressure and/or these other factors are essential for enhanced PG production in coarctation hypertension, and 4) synthesis of all GAG types appears to be affected.
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PMID:Increased proteoglycan synthesis by the cardiovascular system of coarctation hypertensive rats. 206 67

Twelve endocrine variables in blood from a small number of clinically healthy adult women were sampled systematically around the clock and the seasons. Pattern discrimination methods singled out certain hormone values in certain seasons as classifiers for a high vs low risk of developing diseases associated with a high blood pressure. Further evidence in support of such classifiers is obtained on data from adolescent, menstrually cycling young adults and post-menopausal women, here analyzed as pool of series, with the scope of the data from any one age group greatly extended by a resampling procedure, namely, by bootstrapping. This mathematical approach was carried out on data series around the clock and seasons on several hormones as well as systolic and diastolic blood pressure. Classifier roles were strongly supported for plasma aldosterone and thyroid stimulating hormone, originally by an analysis of variance and, in the case of aldosterone, by circannual cosinor analysis and by numerical resampling. Circannual bootstrapping, a procedure recommended for broad routine use as a safeguard for hypothesis testing, was also done for plasma cortisol, dehydro-epi-androsterone sulfate and prolactin, variables for which (parametric) analyses of variance and cosinors did not reveal any difference between groups at high and low cardiovascular risk. In these instances, bootstrapping results are tentative and await further analyses. Results show the ability of circannual bootstrapping to detect outliers. Identification of classifiers provides cost-effective endocrine checks complementing the targeted automatic monitoring of blood pressure. Circannual indices for risk evaluation are, however, costly in several ways since it takes at least a year and quite a few samples to estimate them reliably. Accordingly, we also extended the scope of previous results by the application of an added procedure for circadian bootstrapping. With circadian as well as circannual bootstrapping, we here illustrate a major potential component of a system of chrono-engineering for health maintenance. This system should start with focus on the newborn. The results on adults here analyzed are likely to be more prominent in the neonate, to the extent that they are genetic in origin, yet amenable to modification by the extra-uterine environment.
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PMID:Human mesor-hypertensive chronorisk. 208 92

The effect of magnesium sulfate on ventricular refractoriness and its efficacy for torsade de pointes (TdP) were studied in nineteen dogs. After the administration of quinidine sulfate (30 mg/kg), TdP was induced by ventricular pacing in ten of 19 dogs (52.6%), polymorphic ventricular tachycardia in seven (36.8%), ventricular fibrillation in two (10.5%). Quinidine sulfate caused significant increases in QTc interval, ventricular effective refractory period (ERP) and dispersion of ERP(dERP), and decrease in ERP/QT. Magnesium sulfate significantly increased ERP (p less than 0.01), but it did not change QT interval, resulting in significant increasing of ERP/QT (0.41 +/- 0.05 to 0.61 +/- 0.05, p less than 0.01). It decreased dERP but not significantly. Magnesium sulfate prevented the induction of TdP in eight of 10 dogs (80.0%) (30 mg/kg in four and 60 mg/kg in four). In conclusion, magnesium sulfate has value as first aid therapy for drug-induced TdP. If patients have ischemic heart disease or hypertension, we recommend infusion of magnesium for the initial therapy of TdP.
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PMID:Effect of magnesium sulfate on ventricular refractoriness and its efficacy for torsade de pointes. 209 63

Early chronic sympathectomy does not normalize blood pressure (BP) in genetically hypertensive rats of the Lyon strain (LH). The purpose of this study was to examine the role of the renin angiotensin system (RAS) and vasopressin in the residual hypertension exhibited by LH sympathectomized rats. Chronic sympathectomy was achieved by treating male LH and control normotensive LN rats with guanethidine sulfate between 1 and 13 weeks of age (60 mg/kg daily from day 7 after birth to day 25, 30 mg/kg daily from day 26 to day 70 and 30 mg/kg every other day from day 71 to day 90). At 14 weeks of age, catheters were inserted into the lower abdominal aorta and inferior vena cava via the left femoral artery and vein. After 2 days of recovery, BP was continuously recorded in the conscious freely moving animals during 3 consecutive 1-hour periods: before and after administration of either an angiotensin converting enzyme inhibitor (perindopril 2 mg/kg i.v.) or a selective vascular vasopressin antagonist [beta-mercapto- beta,beta-cyclopentamethylenepropionyl1, O-Me-Tyr2, Arg8-vasopressin, AVPX 10 micrograms/kg i.v.) and finally after conjoint administration of both drugs. At the end of each period, the efficacy of blockade was verified by the disappearance of pressor responses to respective agonists (angiotensin I 150 ng/kg i.v., Arg8-vasopressin 10 ng/kg i.v.). Chronic treatment with guanethidine resulted in the disappearance of pressor responses to tyramine (250 micrograms/kg i.v.) indicating complete functional denervation of the vessels. Under basal conditions, the 1-hour average value of mean BP (MBP) was higher in LH than in LN sympathectomized rats (134 +/- 3 vs 104 +/- 2 mmHg, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Role of renin-angiotensin system and vasopressin in the control of blood pressure in genetically hypertensive rats after sympathectomy]. 212 62


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