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)

Fosinopril is distinguished from other ACE inhibitors by a pharmacokinetic pecularity in the sense that is can be metabolized either by liver or kidney. This was the rationale of the present research the aim of which was to verify if administered to patients with liver cirrhosis the drug was liable to alter global liver function and ability to metabolize drugs. Eight cirrhotic males, mean age 56 years, also suffering from high blood pressure, were studied. In these patients, liver and kidney function tests (BUN, creatinine blood level, serum and urinary electrolytes, creatinine clearance, calcium and phosphor blood level, transaminases, alkaline phosphatase prothrombin time, cholinesterase, gamma-glutamyl-transpeptidase) were carried out at baseline and after 30 days' fosinopril treatment (1 capsule every morning in the fasting state); in addition total functioning liver mass was assessed by the galactose test, and drug-metabolizing capacity by the antipyrine test. Treatment resulted in a significant improvement of pressure values in all patients (p < 0.01) and did not alter liver and kidney function parameters. Besides, no side effects were registered, especially no case of orthostatic hypotension. The antipyrine test was not influenced by fosinopril treatment. Therefore, short-term treatment with this ACE-inhibitor can be concluded to be effective and not to cause additional alterations of liver function in patients with liver cirrhosis.
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PMID:[Evaluation of the total hepatic function after treatment with fosinopril in hypertensive patients with liver cirrhosis]. 772 Mar 55

Cholinomimetic agents increase blood pressure and heart rate via central muscarinic cholinoceptors in various species. It was reported that i.c.v. injection of the muscarinic M1 and M3 cholinoceptor selective antagonist, 4-DAMP (4-diphenylacetoxy-N-methyl-piperidine methiodide), inhibited the pressor response to physostigmine, while the M1 selective antagonist, pirenzepine, was ineffective. In the present study, the involvement of muscarinic M2 cholinoceptors in central cholinergic hypertension and tachycardia was investigated. Physostigmine (10-80 micrograms/kg i.v.), a cholinesterase inhibitor, and oxotremorine (20-40 micrograms/kg i.v.), a direct muscarinic cholinoceptor agonist, caused a dose-dependent increase in blood pressure. Additionally, physostigmine induced dose-dependent tachycardiac responses. I.c.v. administration of the muscarinic M2 cholinoceptor antagonists, AF-DX 116 and methoctramine, inhibited both physostigmine (60 micrograms/kg) and oxotremorine (20 micrograms/kg)-induced pressor responses at their lower doses used in this study (100 nmol/rat and 10 nmol/rat, respectively). These findings indicate the partial involvement of postsynaptic muscarinic M2 cholinoceptors. The higher doses of the antagonists (AF-DX 116,300 nmol/rat and methoctramine 30 nmol/rat) potentiated the blood pressure increase due to physostigmine but did not affect that due to oxotremorine. The physostigmine-induced tachycardiac responses were influenced similarly by these antagonists. These results suggest the presence and tonic influence of presynaptic inhibitory muscarinic M2 cholinoceptors.
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PMID:Central muscarinic M2 cholinoceptors involved in cholinergic hypertension. 811 94

Using a sensory stimulation (startle) paradigm in normotensive and hypertensive rats, we evaluated the contribution of central cholinergic mechanisms to the pathology of hypertension. In normotensive Wistar-Kyoto (WKY) rats, transient airpuff stimuli elicit a complex startle reaction consisting of several behavioral and autonomic components. These include jumping (motor response), an increase in blood pressure (pressor response), an early-trial decrease in heart rate (bradycardia) and a later-trial increase in heart rate (tachycardia). Intracerebroventricular (i.c.v.) administration of cholinergic compounds to WKY rats primarily altered the bradycardia component. Thus, depletion of brain acetylcholine with hemicholinium-3 (5 micrograms/kg i.c.v.) abolished bradycardia responses without significantly affecting the motor response, tachycardia or pretest cardiovascular base-line parameters. Furthermore, enhancement of brain acetylcholine with acetylcholinesterase inhibition (physostigmine, 50 micrograms/kg i.c.v.) enhanced bradycardia in WKY rats. The nonspecific muscarinic antagonist scopolamine and the M1 muscarinic receptor antagonist pirenzepine, but neither the M2 muscarinic antagonist methoctramine nor the nicotinic antagonist hexamethonium, attenuated bradycardia. We conclude that a central M1 muscarinic receptor participates in the control of startle-associated bradycardia in the WKY rat. The spontaneously hypertensive rat does not normally exhibit startle-associated bradycardia. Because i.c.v. physostigmine revealed early-trial bradycardia in this strain, we conclude that a selective central cholinergic deficit contributes to a suppression of startle-associated bradycardia in the spontaneously hypertensive rats.
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PMID:A unique central cholinergic deficit in the spontaneously hypertensive rat: physostigmine reveals a bradycardia associated with sensory stimulation. 813 21

Eptastigmine is a new cholinesterase inhibitor, which may be potentially useful for the symptomatic treatment of Alzheimer's disease. A preliminary evaluation of its pharmacodynamic and pharmacokinetic profiles in the elderly has now been made in 6 healthy subjects (63-84 years of age) given 30 mg eptastigmine as a single oral dose. Blood was collected prior to and 1, 2, 3, 4, 6, 8, and 12 h after eptastigmine administration for measurement of cholinesterase inhibition in plasma and red blood cells and the plasma drug concentrations. The maximum plasma cholinesterase inhibition was 17%, which was reached 2.7 h after treatment. In red cells the maximum inhibition of the enzyme was 29% after 3.8 h. The estimated half-time of cholinesterase recovery was 12.4 h in plasma and 13.6 h in red blood cells. The peak plasma concentration of eptastigmine of 0.86 ng.ml-1 was reached after 1.4 h. Following absorption the drug was rapidly distributed into tissues (t1/2 alpha = 0.44 h) and then eliminated with a half-life of 12.1 h. The drug was well tolerated in all but one subject, who showed bradycardia with hypertension and nausea for about 2 h after the dose. The results indicate that oral administration of eptastigmine to elderly subjects produces long lasting inhibition of cholinesterase activity in plasma and in red blood cells.
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PMID:Pharmacodynamics and pharmacokinetics of eptastigmine in elderly subjects. 829 73

To study acute organophosphorus (OP) poisoning cases, 190 OP-intoxicated cases admitted to Civil Hospital, Ahmedabad, were investigated in depth. The group consisted of subjects ranging from 11 to 60 years of age, with the maximum number of cases in the age group 21-30 years and a male-to-female ratio of 2.1:1. Most of the subjects (71.61%) were partially educated, 24.2% of the cases were illiterate, and only 4.2% of the cases were highly educated. Socioeconomically, 21.1% of the subjects were of low economic status, 52.6% were low middle class, 16.8% were upper middle class, and only 9.5% were upper class. With regard to marital status of the subjects, 98 cases were married and 92 were unmarried. About 67.4% of the cases had the intention of committing suicide, 16.8% of the cases were the result of occupational exposure, and 15.8% of the cases were from accidental poisoning. Social and domestic problems (37.5%), marital friction (15.6%), financial stress (15.6%), love affairs (14.1%), job problems (10.9%), chronic illness (4.7%), and failure in examination (1.6%) were observed as the precipitating factors. Muscarinic manifestations such as vomiting (96.8%), nausea (82.1%), miosis (64.2%), excessive salivation (61.1%), and blurred vision (54.7%) and CNS manifestations such as giddiness (93.7%), headache (84.2%), disturbances of consciousness (44.2%), and typical pungent odor from mouth and clothes (77.9%) were the main presenting symptoms. Cardiac manifestations such as sinus tachycardia (25.3%), sinus bradycardia (6.3%), and depression of ST segments with T-wave inversion (6.3%) were observed electrocardiographically, with hypertension (10.5%) and muscular twitching in some (2.1%) cases. Biochemical changes such as albuminuria (12.6%) and azotemia (18.9%) with inhibition of acetylcholinesterase enzyme activity in blood were recorded in 78.9% of the cases. About 89.5% of the cases recovered completely, 4.2% of the cases absconded after partial recovery, and 6.3% of the cases died. The mortality rate (6.3%) depended on various factors such as the organophosphorus compound consumed, the amount ingested, the time interval for hospitalization, and the general health of the patient. Chances of recovery were higher when the patient was hospitalized at the earliest indication.
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PMID:A clinical, biochemical, neurobehavioral, and sociopsychological study of 190 patients admitted to hospital as a result of acute organophosphorus poisoning. 832 67

A 45-year-old man was hospitalized because of acute hepatitis. His serum cholinesterase (ChE) was below 10 IU/l (normal range: 105-240 IU/l) during the disease course and after his recovery. The patient was suspected of having familial hypocholinesterasemia. His family members were healthy except that his father had hypertension and gall stones. Analysis of ChE gene in the propositus and his family revealed three point mutations at nucleotides 298 (CCA to TCA), 1,410 (CGT to CGG) and 1,615 (GCA to ACA). The first mutation caused an amino acid change at codon 100 from proline to serine, which was a new mutation not previously reported, but the second one was a silent mutation. The third mutation resulted in an amino acid alteration from alanine to threonine at codon 539 in exon 4 of the ChE gene. The mode of transmission of these mutations is described.
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PMID:Familial hypocholinesterasemia found in a family and a new confirmed mutation. 905 91

The influence of pregnancy-induced hypertension (pre-eclampsia) on muscarinic cholinergic receptors and on acetylcholinesterase (AChE) activity was investigated using frozen sections of the umbilical artery and vein. Pre-eclamptic patients undergoing Caesarean delivery and normotensive pregnant control woman undergoing Caesarean delivery with similar parity, gestation length and age were examined. Muscarinic cholinergic receptors were assayed in frozen sections of the umbilical artery and vein by a radioligand binding assay technique, using [3H]-N-methyl scopolamine (NMS) as a ligand. AChE was demonstrated with a histochemical technique associated with microdensitometry. [3H]-NMS was specifically bound to sections of both umbilical artery and vein in a manner consistent with the labelling of muscarinic cholinergic receptors. The affinity of the radioligand was similar in the two vessels, whereas the maximum density of binding sites (Bmax) was higher in the umbilical vein than in the artery. A faint AChE reactivity was observed in the tunica media of both umbilical artery and vein. In pre-eclampsia, a loss of [3H]-NMS binding sites not accompanied by changes in the affinity of radioligand was found. The decrease of muscarinic cholinergic receptors involved to a greater extent the umbilical artery than the vein. No differences in AChE activity were found at the level of umbilical artery and vein between control and pre-eclamptic subjects. These findings suggest that pre-eclampsia is characterized by a loss of muscarinic cholinergic receptors in the umbilical circulation not accompanied by changes of the acetylcholine catabolizing enzyme AChE. It is possible that the decreased density of vascular muscarinic cholinergic receptors in pregnancy-induced hypertension contribute to the increased resistance of the umbilical circulation occurring in pre-eclampsia.
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PMID:Muscarinic cholinergic receptors and acetylcholinesterase activity in umbilical artery and vein in pregnancy-induced hypertension (pre-eclampsia). 938 71

The practical pharmacological approaches currently available to palliate the cognitive and functional losses in early Alzheimer's disease (AD) include cholinesterase inhibitors (ChEI), antioxidants (e.g., vitamin E), anti-inflammatory agents, estrogen, seligiline, vasoactive agents, and ginkgo biloba. Reviewing available data on these therapies and using models from medical illnesses such as cancer and hypertension, we highlight the urgent need for evaluating combination therapies in early AD.
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PMID:Combination therapy for early Alzheimer's disease: what are we waiting for? 977 22

The present study was designed as a hospital-based, group-matched, case-control investigation into the risk factors associated with age-related cataract in central India. The study included 262 cases of age-related cataract and an equal number of controls. A total of 21 risk factors were evaluated: namely, low socioeconomic status (SES), illiteracy, marital status, history of diarrhoea, history of diabetes, glaucoma, use of cholinesterase inhibitors, steroids, spironolactone, nifedipine, analgesics, myopia early in life, renal failure, heavy smoking, heavy alcohol consumption, hypertension, low body mass index (BMI), use of cheaper cooking fuel, working in direct sunlight, family history of cataract, and occupational exposure. In univariate analysis, except marital status, low BMI, renal failure, use of steroids, spironolactone, analgesics, and occupational exposure, all 14 other risk factors were found significantly associated with age-related cataract. Unconditional multiple logistic regression analysis confirmed the significance of low SES, illiteracy, history of diarrhoea, diabetes, glaucoma, myopia, smoking, hypertension and cheap cooking fuel. The etiological role of these risk factors in the outcome of cataract is confirmed by the estimates of attributable risk proportion. The estimates of population attributable risk proportion for these factors highlight the impact of elimination of these risk factors on the reduction of cataract in this population.
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PMID:Risk factors for cataract: a case control study. 1021 5

The acetylcholinesterase inhibitor, soman, induces marked and sustained hypertension and tachycardia associated with a convulsive syndrome in rats. The aims of the present study were to distinguish between the cardiovascular and convulsant effects of soman and to determine whether the maintenance of the soman-induced hypertension and tachycardia depends solely on a central muscarinic effect. To this end, using a computerised analysis of blood pressure (BP) in conscious freely moving rats, we examined the consequences on the increase in mean BP (MBP) and heart rate (HR) induced by soman (60 micrograms/kg, i.v.) of 1) a pre-treatment with the anticonvulsant drug diazepam (3 mg/kg, i.v.) and 2) atropine sulphate (10 mg/kg, i.v.) administered 10 or 60 min after the intoxication. Pretreatment with diazepam prevented the convulsions, assessed by electroencephalogram (EEG) recording, but modified neither the magnitude nor the kinetics of the pressor and tachycardic effects of soman (delta MBP = 74 +/- 2 and 73 +/- 5 mmHg, delta HR = 69 +/- 10 and 79 +/- 7 bpm, maximum MBP = 186 +/- 3 and 182 +/- 6 mmHg, maximum HR = 545 +/- 9 and 522 +/- 16 bpm in solvent- (n = 8) and diazepam- (n = 8) pre-treated rats, respectively). Whatever its time of administration, atropine sulphate fully and immediately reversed the rise in BP induced by soman. The soman-induced tachycardia was also suppressed by atropine administered 10 min after soman whereas it persisted when atropine was injected 60 min after the intoxication. These results show that the cardiovascular effects of soman can occur independently of the convulsive syndrome and that the maintenance of the soman-induced hypertension depends entirely on a permanent central muscarinic stimulation.
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PMID:Soman-induced hypertension in conscious rats is mediated by prolonged central muscarinic stimulation. 1045 88


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