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)

Thirteen men, age 60 +/- 2 years (mean +/- SEM) with mild hypertension, 151 +/- 4/95 +/- 3 mm Hg, completed a randomized, double-blind, placebo-controlled crossover trial of ketanserin therapy. In comparison to placebo, ketanserin treatment at 40 mg bid for 6 weeks lowered systolic and diastolic blood pressure, 148 +/- 4/92 +/- 3 vs. 140 +/- 6/86 +/- 3 mm Hg, P = 0.19/0.02. The rate of platelet aggregation in response to ADP and epinephrine was unchanged while the response to serotonin was greatly diminished. Neither the systemic pressor response nor the pupillary mydriatic response to phenylephrine was significantly altered. Plasma norepinephrine concentration declined significantly. Ketanserin reduced blood pressure, particularly the diastolic component, in elderly men with mild hypertension. While antagonism of serotonin's effects on platelet aggregation was evident, blockade of alpha 1-receptor-mediated events was not apparent. The results suggest that during chronic therapy the antihypertensive effects of ketanserin were mediated by serotonergic blockade and a possible lytic effect on sympathetic drive. The dual effects of ketanserin on blood pressure and platelet aggregation may be beneficial in reducing cardiovascular complications in hypertensive patients.
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PMID:Effects of ketanserin on blood pressure and platelet aggregation in elderly men with mild hypertension. 341 5

Platelet aggregation was studied in patients with high and stable arterial hypertension that was mostly associated with the malignant syndrome, and the effect of PGE2 introduced into the blood flow as repeated intravenous infusions on platelet activity was assessed. The addition of low-dose inductor produced the greatest changes in platelet aggregation following platelet exposure to different ADP doses in the patients, as compared to normal subjects. Stimulation with 0.1 mumol ADP produced a 7-fold increase in platelet aggregation in hypertensive patients, as compared to the controls. Repeated administration of 1.2-1.5 mg PGE2 normalizes cell sensitivity to ADP. Mean arterial BP dropped by 15-45 mm Hg during the infusions and remained low for several days afterwards.
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PMID:[Platelet aggregation in severe and malignant forms of hypertension: effect of treatment with prostaglandin E2]. 347 7

The purpose of this study was to test the effects of a low-fat, low-cholesterol diet on serum lipids, platelet aggregation, thromboxane formation and blood pressure. Fifteen hyperlipidemic males with normal blood pressure were treated for 2 weeks. Resting supine blood pressure, total serum cholesterol, HDL-cholesterol, the ratio of total cholesterol/HDL-cholesterol and triglycerides all were significantly reduced. The maximum aggregation and velocity of aggregation for isolated platelets stimulated with either ADP or collagen was significantly reduced. Thromboxane formation during 5 min of platelet aggregation with collagen or ADP was also significantly reduced. These results have important implications for hypertension and atherosclerotic cardiovascular disease.
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PMID:Effects of a low-fat, low-cholesterol diet on serum lipids, platelet aggregation and thromboxane formation. 347 54

Blood platelets of patients with essential hypertension display signs of both increased sensitivity in vitro to aggregating stimuli believed to contribute to thrombosis and of activation in vivo possibly expressing the release of vasoactive products. The mean features of the modified platelet profile in hypertension include an increased alpha 2-adrenergic receptor density, an enhanced rate of adhesion/aggregation in particular in response to ADP and arachidonic acid, a greater sensitivity for thrombin and adrenaline to stimulate increases in cytoplasmic-free Ca2+, increased resting levels of cytoplasmatic-free Ca2+, a reduced content of serotonin often combined with a defective uptake mechanism, a facilitated efflux rate of noradrenaline, an exaggerated release reaction in vivo as indicated by the increased plasma levels of Beta-thromboglobulin and a shortened platelet life span. These changes occur to various extents in some, but not all, hypertensive patients and are not always strictly related to the degree of blood pressure increase. On the contrary, platelet cyclooxygenase and thromboxane synthetase activity are in the normal range.
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PMID:Blood platelets in human essential hypertension. 353 21

A study was carried out in 16 patients with moderately severe hypertension to investigate the effects of nifedipine, given alone or combined with a diuretic, on blood pressure and on renal and platelet function. After 4 weeks on placebo, patients were randomized to receive treatment for 6 weeks with either 20 mg, nifedipine twice daily or 25 mg mefruside once daily on a double-blind, double-dummy basis. All patients then received treatment for a further 6 weeks with a combination of the two drugs in the same dosage as before. The results of blood pressure measurements and laboratory investigations during the three phases of the study showed that significantly better blood pressure control was achieved with nifedipine alone than with mefruside alone. Mefruside had an additional hypotensive effect when added to nifedipine. There was no significant change in the renal blood flow or glomerular filtration rate, with a satisfactory control of blood pressure. There was also no detectable change in platelet aggregation with increasing concentrations of ADP and ristocetin. An adaptive mechanism could be responsible for the apparent lack of change compared with single dose studies.
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PMID:Effect of nifedipine and mefruside on renal function and platelet function in hypertensive patients. 362 89

Stroke-prone spontaneously hypertensive rats (SHRSP) were treated with food admixed, 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-4-([4-(2-methoxyphenyl)-1- piperazinyl]methyl)isoquinoline (Ro 22-4839), a novel cerebral circulation improver, for a period of 15 weeks starting from 5 weeks of age at an average daily dose of 30.6 or 66.0 mg/kg. As compared with normotensive Wistar Kyoto rats, SHRSP in the control group rapidly developed severe hypertension (244 mmHg at the end of the experiments) accompanied with deterioration of cardiovascular parameters including left ventricular hypertrophy, reduction in pumping ability and increase in peripheral vascular tone. At 20 weeks of age (i.e. at the end of experiments), 75% of SHRSP developed stroke signs and concomitant cerebral edema evidenced by the increases in water and sodium contents in the brain. These stroke symptoms were accompanied with a profound externalized shape change of erythrocytes after in vitro treatment with Ca2+ and ionophore A23187, an increased plasma level of thiobarbituric acid reacting substance (TBARS), a measure of lipid peroxides, and a decreased sensitivity of platelets to ADP. The long-term treatment with Ro 22-4839 prevented the progress of stroke and cerebral edema, although the deteriorated cardiovascular parameters were not prevented by the treatment. This compound was also found to prevent the hypersusceptibility of erythrocyte membrane to Ca2+-ionophore and Ca2+, the hypoaggregability of platelets and the elevated plasma TBARS in SHRSP. These results indicate that the beneficial effects of Ro 22-4839 in SHRSP may be attributable to its calmodulin antagonistic and anti-lipid peroxidative actions but not to its hypotensive action.
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PMID:Preventive effects of the cerebral circulation improver 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-4-([4-(2-methoxyphenyl)- 1-piperazinyl]methyl)isoquinoline on stroke symptoms in stroke-prone spontaneously hypertensive rats. 367 71

Forty-six elderly patients (mean age 60 years) suffering from diabetes mellitus (DM), or essential or arteriosclerotic hypertension (HT) were divided into 4 groups. Group 1 served as a control, group 2 was administered 1500 mg niceritrol, group 3 was administered 162 mg acetylsalicylic acid (ASA), and group 4 was administered both 1500 mg niceritrol and 162 mg ASA/day for 8 weeks. Niceritrol lowered serum levels of beta-lipoprotein and total cholesterol and increased HDL cholesterol, usually in 8 weeks. ASA did not affect the lipid-lowering effects of niceritrol. Platelet aggregation induced by epinephrine (1 microgram/ml), collagen (1 microgram/ml), and ADP (2 microM) was depressed in groups 2, 3 and 4. Degrees of depression were higher in groups administered ASA (groups 3 and 4) than in the group administered niceritrol alone (group 2). Plasma fibrinogen levels were lowered in groups administered niceritrol (groups 2 and 4) in 8 weeks. Apparent whole blood viscosity measured at shear rates of 37.6/s and 376/s was improved only in group 4 in 8 weeks, while hematocrit did not change during the study. Because flushing, the most frequent side effect of niceritrol, can be easily controlled by a low dose of ASA, and because the combination of the 2 drugs has some beneficial effects on blood rheology, this combination is considered worthwhile for treatment and prevention of atherosclerosis.
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PMID:The effects on lipids, blood viscosity and platelet aggregation of combined use of niceritrol (Perycit) and a low dose of acetylsalicylic acid. 400 83

Effects of CV-2619 (10 and 30 mg/kg/day, p.o.) or ubiquinone-10 (Q-10, 10 mg/kg/day, p.o.) treatment for 5 weeks on systolic blood pressure (SBP) and myocardial energy metabolism were studied in spontaneously hypertensive rats of 20 weeks of age. The systolic blood pressure was about 205 mmHg at the start of the experiment, and a slight increase was noted thereafter in the control (vehicle) group. CV-2619, but not Q-10, inhibited the increase in the blood pressure. At 25 weeks of age, cardiac hypertrophy was noted to the same extent in either treated group. Myocardial contents of glycolytic intermediates (glycogen, glucose, pyruvate and lactate) and creatine phosphate (Cr-P), ATP, ADP, and AMP were not significantly influenced by CV-2619 or Q-10 treatment. CV-2619, however, significantly increased the energy charge, an index of myocardial energy state, with higher dose and lowered the lactate/pyruvate ratio with either dose. These results suggest that CV-2619 has a mild antihypertensive effect and improves the myocardial energy state in the hypertrophied heart during the sustained phase of hypertension in SHR rats.
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PMID:[Effects of 2,3-dimethoxy-5-methyl-6-(10'-hydroxydecyl)-1,4-benzoquinone (CV-2619) on myocardial energy metabolism in the hypertrophied heart of spontaneously hypertensive rats]. 629 97

Prostacyclin (PGI2) was administered by inhalation (50 micrograms/min) and intravenous infusion (15 ng/kg/min) in 5 healthy male volunteers. Irrespective of the route of administration this substance was shown to have no effects on respiratory indices studied, whereas a significant inhibition of ADP-induced platelet aggregation and a fall in vascular resistance could be demonstrated. Mainly because of the latter action it is suggested that PGI2, or a stable synthetic analogue, might become a potent drug in various pathological conditions, in which hypertension of various causes is a problem.
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PMID:Pulmonary and antiaggregatory effects of prostacyclin after inhalation and intravenous infusion. 638 93

Islet-activating protein (IAP), pertussis toxin, is an oligomeric protein composed of an A-protomer and a B-oligomer. There seem to be at least two molecular mechanisms by which IAP exerts its various effects in vivo and in vitro. On the one hand, some of the effects were not significantly affected by acetamidination of the epsilon-amino groups of the lysine residues in the molecule. These include the activities in vitro (1) catalyzing ADP-ribosylation of one of the membrane proteins directly, (2) enhancing membrane adenylate cyclase activity in C6 cells, (3) reversing receptor-mediated inhibition of insulin or glycerol release from pancreatic islets or adipocytes, respectively, and the activities in vivo (4) inhibiting epinephrine-induced hyperglycemia, (5) potentiating glucose-induced hyperinsulinemia, (6) reducing hypertension and increasing the heart rate in genetically hypertensive rats. These activities are concluded to develop as a result of ADP-ribosylation catalyzed by the A-protomer which is rendered accessible to its intramembrane substrate thanks to the associated B-oligomer moiety. Thus, neither the enzymic activity of the A-protomer nor the transporting activity of the B-oligomer needs free amino groups of the lysine residues in the IAP molecule. On the other hand, additional effects of IAP, such as (1) mitogenic, (2) lymphocytosis-promoting, (3) histamine-sensitizing, (4) adjuvant and (5) vascular permeability increasing, were markedly suppressed by acetamidination of the intrapeptide lysine residues. The free epsilon-amino group of lysine would play an indispensable role in the firm (or divalent) attachment of the B-oligomer of IAP to the cell surface that is responsible for development of these activities.
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PMID:Dual mechanisms involved in development of diverse biological activities of islet-activating protein, pertussis toxin, as revealed by chemical modification of lysine residues in the toxin molecule. 638 83


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