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

In a double-blind controlled trial, 91 middle-aged and elderly women with mild to moderate hypertension who were not on antihypertensive medication were randomly assigned to treatment with magnesium aspartate-HCl (20 mmol Mg/d) or placebo for 6 mo. Magnesium aspartate-HCl in the given dose was well-tolerated and was not associated with an increased frequency of diarrhea compared with placebo. At the end of the study, systolic blood pressure had fallen by 2.7 mm Hg (95% CI -1.2, 6.7; P = 0.18) and diastolic blood pressure by 3.4 mm Hg (1.3, 5.6; P = 0.003) more in the magnesium group than in the placebo group. Blood pressure response was not associated with baseline magnesium status, as measured by dietary magnesium intake and urinary magnesium excretion. Urinary magnesium excretion in the magnesium group increased by 50% during the intervention period. No changes were seen in other biochemical indexes, including serum concentrations of total and high-density-lipoprotein cholesterol. The findings suggest that oral supplementation with magnesium aspartate-HCl may lower blood pressure in subjects with mild to moderate hypertension.
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PMID:Reduction of blood pressure with oral magnesium supplementation in women with mild to moderate hypertension. 801 27

Abbott-72517 is an inhibitor of human renin and is being investigated for the treatment of hypertension. It is an orally bioavailable candidate which is being developed for oral as well as intravenous use. The preclinical development of this molecule involved studies to evaluate irritation at the site of injection in an animal model. Several formulation variables such as drug concentration, types of buffer (citrate or acetate), addition of cosolvent (ethanol) to enhance drug solubility, and tonicity modifiers such as glycerin or mannitol were evaluated. Additionally, in vitro formulation--whole blood hemolysis and plasma precipitation studies were conducted. Based on these studies, a liquid formulation containing 1.2 mg/mL Abbott-72517.HCl as base, 0.01M citrate buffer, pH 3.7, in 0.45% sodium chloride containing 2.5% mannitol was recommended for preclinical studies. Various processing and administration parameters were evaluated including filter qualification and compatibility of the drug with typical infusion fluids and administration sets. The liquid formulation was further characterized for physical and chemical stability. It was shown that it has acceptable stability at ambient temperature. Based on the accelerated temperature storage results, T90 at 25 degrees C is > 1 year for the ready-to-use liquid formulation. Additionally, a lyophilized version of the liquid formulation was evaluated.
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PMID:Parenteral formulation development of renin inhibitor Abbott-72517. 803

The safety and efficacy of an extended-release form of diltiazem HCl (diltiazem XR) in patients 55 years or older with mild-to-moderate essential hypertension were examined in a multi-center, double-blind, randomized, placebo-controlled, parallel-group study involving 350 patients with supine diastolic blood pressure (DBP) between 95 mm Hg and 114 mm Hg. Patients were randomized to a once-daily dose of diltiazem XR (240 mg) or placebo; 261 patients received diltiazem XR and 89 received placebo. After 4 weeks, the dose was doubled (to 480 mg) in patients whose supine DBP was > 90 mm Hg, and treatment was continued for another 4 weeks. Diltiazem XR consistently reduced blood pressure (BP) in the study population. At end-point, the mean reduction in supine DBP was 8.65 mm Hg in the diltiazem XR group and 2.75 mm Hg in the placebo group (P < 0.0001). Subgroup analysis confirmed the efficacy of diltiazem XR in men, women, patients between the ages of 55 and 64 years, patients 65 years or older, and non-black patients. Other BP values (supine systolic, standing diastolic, and standing systolic) also were significantly reduced in patients treated with diltiazem XR. BP reduction (supine DBP < or = 90 mm Hg or by > or = 10 mm Hg) was achieved in 58% of patients receiving diltiazem XR compared with 27% of patients receiving placebo. Decreases in apical heart rate were minimal and similar in both groups. No significant differences were noted in adverse events in the diltiazem XR and placebo groups: 36.4% of patients in the diltiazem XR group and 37.1% in the placebo group had no adverse experiences, and 63.6% and 62.9%, respectively, had at least one adverse event. Physical examination findings and laboratory values were clinically unremarkable and comparable in the diltiazem XR and placebo groups. Diltiazem XR given once daily at doses of 240 mg and 480 mg was safe and effective in lowering blood pressure in mature and elderly patients with mild-to-moderate hypertension.
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PMID:Blood pressure control with diltiazem XR, a novel extended-release formulation of diltiazem HCl, in mature and elderly hypertensive patients. 806 17

Injuries caused by compression of spinal nerve roots are frequently encountered clinically. Experimental studies show that several different factors affect the pathophysiologic changes that occur after these injuries. However, the effect of hypertension in conjunction with graded compression of spinal nerve roots is yet unclear. A previously established porcine model was employed, in which the spinal nerve roots were exposed and compressed by an inflatable balloon. Impulse propagation across the compressed nerve segment was studied by the recording of efferent and afferent nerve action potentials, and nerve conduction velocity. The systemic blood pressure was increased by administration of Neo-Synephrine hydrochloride (phenylephrine HCl) (Winthrop Pharmaceuticals, New York, NY) and elevated 40 +/- 5 mm Hg above the normal (100 +/- 5 mm Hg), and electrophysiologic baseline values were recorded. The spinal nerve roots were then compressed for 2 hours with either 0 (control), 50, 100, or 200 mm Hg. The balloon was deflated and the nerve roots were allowed to recover for 1.5 hours. Impulse propagation was studied every 15 minutes and hypertension was maintained throughout the experiment. The results showed no significant changes of the efferent and afferent nerve action potentials at 0.50 or 100 mm Hg. At 200 mm Hg, efferent and afferent nerve action potentials decreased rapidly and were almost abolished within 20 minutes of compression. Some but not significant recovery was seen of the nerve impulse. Compared to data from normotensive pigs in an earlier experiment, the current study showed that hypertension significantly decreases the susceptibility of the spinal nerve roots to compression at and below 100 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of induced hypertension and acute graded compression on impulse propagation in the spinal nerve roots of the pig. 823 28

We performed this study to examine the presence of a kallikrein-kinin system in rat fetal and maternal tissues. Uteri and placenta from Wistar pregnant and nonpregnant rats were perfused to eliminate blood, and fetal membranes were washed several times with saline. Amniotic fluids were obtained without blood contamination by amniocentesis from eight rats. The different samples were homogenized and centrifuged (2000g during 20 minutes), and the supernatant was incubated with dog kininogen and 0.1 mol/L Tris-HCl buffer (pH 8.5) in the presence of peptidase inhibitors. Kinins released were measured by radioimmunoassay. Kininogenase activity was found in rat uteri, placental vessels, amniotic fluids, and fetal membranes. The enzymes were present in active but mostly in inactive forms. The kallikrein-like enzymes found in the different preparations and rat urinary kallikrein used as control had similar molecular weights, immunologic characteristics, and inhibition profiles with protease inhibitors. We conclude that kallikrein-like enzymes are present in rat organs of reproduction. These data suggest that kinins released locally may act as paracrine hormones in the regulation of blood pressure during pregnancy.
Hypertension 1994 Jan
PMID:Biochemical evidence of a kallikrein-like activity in rat reproductive tissues. 828 57

The fine structure of vascular smooth muscle cells from large mesenteric arteries of adult (28 weeks) spontaneously hypertensive rats and Wistar-Kyoto rats was studied using scanning electron microscopy (SEM). The effect of the digestion method for SEM on tissue size and smooth muscle cell size was also studied using morphometric analysis. A significant reduction in cell size (42-43%) was present after critical point drying, based on the reduction in volume to surface ratio of smooth muscle cells. However, percent change of volume density and volume to surface ratio of smooth muscle cells after digestion and after critical point drying, was similar between the hypertensives and normotensives. Most of the tissue shrinkage occurred during the digestion process to remove the connective tissue. Overall tissue shrinkage due to the digestion method involving OsO4/HCl and subsequent processing for SEM, based on changes in the thickness of the medial wall, was similar between arteries from hypertensive (34.7%) and normotensive (31.4%). After compensating for the shrinkage, vascular smooth muscle cells from hypertensive animals were found to have a wider somal region (5.94 microns) than those from the normotensives (5.46 microns), suggesting cellular hypertrophy. We conclude that a significant reduction in size of tissue and smooth muscle cells took place when arteries were processed for SEM. For comparative study of vascular changes in hypertension involving SEM, cellular shrinkage due to processing should be included in the calculations in order to provide a reasonable estimate of the alterations.
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PMID:Scanning electron microscopy of vascular smooth muscle cells from spontaneously hypertensive rats. 831 86

A number of studies have shown an antihypertensive effect for high-calcium diets, but others have found no effect or, even a prohypertensive effect. Because of these disparate results, studies were conducted in spontaneously hypertensive rats (SHR) fed either a normal calcium diet (1.0% calcium) or a high-calcium diet (4.0% calcium) with or without verapamil HCl (50 mg/kg body weight) from ages 5 to 12 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured by indirect tail cuff method. During the analysis of the electrolytes and vasoactive hormones monitored in this study, it was found that rats fed high-calcium diet had significantly elevated serum ionized and total calcium and calcium excretion. Systolic blood pressure for the verapamil-normal calcium diet (week 5, 148 +/- 4 mm Hg; week 7, 162 +/- 4 mm Hg) did not differ significantly from that of normal calcium diet (week 5, 152 +/- 2 mm Hg; week 7, 160 +/- 1 mm Hg). The high-calcium diet potentiated the development of hypertension, i.e., SBP was (157 +/- 2 mm Hg) on the 5th week and (174 +/- 4 mm Hg) on the 7th week. Conversely, verapamil high-calcium diet prevented the development of hypertension (week 5, SBP was 139 +/- 4 mm Hg; week 7, SBP was 146 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High-calcium diet in spontaneously hypertensive rats: intervention with calcium antagonist verapamil. 847 48

Although cocaine abuse has been associated with an increased incidence of cerebrovascular accident, the underlying mechanisms are unknown. In this study we have investigated the effects of cocaine upon the autoregulation of local cortical blood flow (lCBF) during hypertension. Hypertension was induced in conscious rats by intravenous infusion of angiotensin-II (5 micrograms/ml; 0.5-2.5 ml/h), and animals were subsequently injected IV with either cocaine-HCl (5 mg/kg) or saline, prior to the measurement of lCBF of glucose utilization (lCGU) using [14C]-iodoantipyrine or [14C]-2-deoxyglucose quantitative autoradiography, respectively. Hypertension alone (< 155 mmHg) did not significantly alter lCBF in any cortical areas examined. However, at higher mean arterial blood pressure (MABP), lCBF increased focally (+265%) in parietal cortex. Cocaine did not alter lCBF in normotensive animals, but with increasing levels of hypertension (MABP > 145 mmHg), all cocaine-treated rats showed focal increases (200-400%) in lCBF in parietal cortex. Glucose use remained relatively unaffected in all treatment groups. This hyperaemia in cocaine-treated rats at MABP below the normal upper limit of autoregulation may provide a mechanism to explain haemorrhagic stroke in cocaine abusers.
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PMID:Acute cocaine alters cerebrovascular autoregulation in the rat neocortex. 849 81

To characterize alterations of renal vessels occurring during systemic hypertension elicited in rats by 5, 10, and 25 days of treatment by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME)(20 mg/kg daily), preglomerular vasculatures, consisting of arcuate arteries and their branches, interlobular arteries, and afferent arterioles, were isolated by HCl maceration. Blockade of nitric oxide synthase significantly increased tail-cuff systolic blood pressure by 21 +/- 2% and 42 +/- 3% after 5 and 25 days, respectively. Medias of hypertensive arcuate arterial branches and interlobular arteries but not of afferent arterioles had focal deposits of Sudan black-positive lipid droplets. At 25 days, vessel wall thickness increased by 72 +/- 6% along the sudanophilic areas. Immunostaining of sudanophilic lesions with a panel of antibodies unveiled medial cell proliferation, macrophage invasion, immunoreactive vascular cell adhesion molecule-1, and low-density lipoprotein. The frequency of sudanophilic lesions increased with time to affect 26 +/- 2% and 36 +/- 3% of arcuate arterial branches and interlobular arteries, respectively, at 25 days. Hypertensive L-NAME-treated rats developed glomerular injury probed by albuminuria and glomerular immunostaining for alpha-smooth muscle actin. Administration of the nonselective endothelin antagonist bosentan (30 mg/kg daily) blunted the development of sudanophilic lesions during L-NAME treatment without affecting arterial hypertension or degree of glomerular injury. Therefore, L-NAME hypertension leads to rapid development of focal, inflammatory, proliferative, and sudanophilic lesions along preglomerular vessels, suggesting atherosclerosis-like processes. Furthermore, endothelin is a likely mediator in the development of these lesions.
Hypertension 1996 Mar
PMID:Preglomerular sudanophilia in L-NAME hypertensive rats: involvement of endothelin. 869 42

Patients with hypertension have a characteristic circadian pattern of blood pressure (BP) variability in a 24-h period, characterized by a wide range while awake and active, and a narrower range during sleep and inactivity. Blood pressure in the untreated hypertensive individual declines by approximately 10% to 20% during sleep compared with the mean awake BP values. Early in the morning (assuming a typical day-night activity cycle), the BP rises sharply on awakening, when physical and mental activities increase. Antihypertensive therapy has been traditionally dosed in the morning after awakening, and in recent years most of the newly developed antihypertensive agents have been once-daily, long-acting preparations. However, theoretically, this pattern of drug dosing may be suboptimal since pharmacodynamic activity is attenuated at the end of the dosing period, when a large rise in BP may occur. Presently, only a few studies have been performed to evaluate the effects of nocturnal dosing of standard long-acting drugs. Consequently, we undertook an assessment of the effects of a new formulation of verapamil--controlled onset extended release verapamil HCl (COER-24)--that is dosed nocturnally and has a controlled onset of delivery (4 to 5 h postdose) and an extended release for the remainder of the dosing period. Through ambulatory BP monitoring, evaluation revealed that this verapamil formulation produced changes in BP that followed the circadian rhythm of BP: lower reductions during sleep, when the BP is intrinsically lowest, and appropriately larger reductions during the early morning and daytime hours, when ambulatory BP values accelerate and plateau to their highest levels. These data demonstrate that it is possible to design antihypertensive therapy for once-nightly dosing, thereby providing a chronotherapeutic regimen for patients with hypertension.
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PMID:A chronotherapeutic approach to the management of hypertension. 872 14


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