Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0038454 (stroke)
147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nesiritide (human recombinant B-type natriuretic peptide) binds to receptors in the vasculature, kidney, and other organs to mimic the actions of endogenous natriuretic peptides. Intravenous infusion of nesiritide has been studied in more than 1,700 patients with acute decompensated heart failure (HF). Nesiritide causes potent, dose-related vasodilation that is rapid in onset and sustained for the duration of drug infusion. There is balanced arterial and venous dilation as reflected by decreases in systemic vascular resistance, systemic arterial pressure, pulmonary capillary wedge pressure, right atrial pressure, and mean pulmonary arterial pressure. Vasodilation occurs without a change in heart rate and is associated with increases in stroke volume and cardiac output. Nesiritide may promote diuresis because of a direct natriuretic action, increased cardiac output, and/or decreased aldosterone levels. In patients hospitalized for decompensated HF, nesiritide improves symptoms and is well tolerated. The major adverse effect is dose-related hypotension. Nesiritide is thus an attractive new vasodilator that should be valuable in the treatment of patients hospitalized for acute decompensated HF.
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PMID:Nesiritide for the treatment of decompensated heart failure. 1126 55

A quantitative trait locus on chromosome 5 in the rat is linked to sensitivity to brain ischemia in the stroke-prone spontaneously hypertensive rat (SHRSP). The genes encoding atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) that map to this location have been excluded as candidate genes. We examined dishevelled-1 (DVL-1) as a further candidate gene. DVL-1 had not yet been identified in the rat, but Anp, Bnp, and DVL-1 map to the homologous regions of the rat chromosome 5 quantitative trait locus in both mice and man. Furthermore, DVL-1 is involved in the Notch signalling system, which plays a role in the disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the symptoms of, which include ischaemic stroke. We show with radiation hybrid mapping that rat DVL-1 indeed maps to chromosome 5, where it is positioned immediately next to microsatellite marker D5Rat49. We sequenced the complete coding sequence and a large part of the intronic genomic sequence for the SHRSP strain and its reference Wistar-Kyoto strain. The DVL-1 sequence in the two strains was identical. Our results essentially exclude the DVL-1 gene as the cause for sensitivity to cerebral ischaemic insult in this rat model of stroke.
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PMID:Mapping and sequencing rat dishevelled-1: a candidate gene for cerebral ischaemic insult in a rat model of stroke. 1135 32

Adrenomedullin is a potent endogenous vasodilating and natriuretic peptide that is similar in structure to calcitonin gene-related peptide (CGRP). The gene involved in the synthesis of adrenomedullin has been localized to a single locus on chromosome 11, with specific sites on the genome to regulate transcription. Adrenomedullin is normally found in human plasma and in other organs. It is thought that one of the clearance sites for this peptide is in the pulmonary circulation. Endothelial cells are assumed to be one of the major sources of plasma adrenomedullin. Adrenomedullin is an important factor in regulating local and systemic vascular tone, by its activity as an autocrine/paracrine and circulating hormone. Depending on the site of action, adrenomedullin seems to bind to a CGRP receptor and send signals by either cyclic adenosine monophosphate or nitric oxide. From the results of experiments in animals, it has become clear that adrenomedullin's effects are species-specific. However, what is commonly seen with adrenomedullin is peripheral vasodilatation, a positive inotropic action, increased cardiac output, and increased stroke volume. In addition, adrenomedullin has actions in the brain, lungs, and kidneys to regulate regional hemodynamics. With these activities defined, recent studies have suggested a potential therapeutic role for adrenomedullin.
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PMID:Adrenomedullin: a vasoactive and natriuretic peptide with therapeutic potential. 1172 67

This study was to investigate the relationship between circadian blood pressure (BP) variation and circadian variation of neurohumoral factors during the acute phase of stroke. We studied 17 patients with cerebral infarction in 16 and cerebral hemorrhage in one. We performed 24-hour ambulatory BP monitoring and examined plasma renin activity (PRA), catecholamine, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endothelin 1 (ET1) and prothrombin fragment 1+2 (PT F1+2) and urinary catecholamine. Our result showed that the circadian variation of BP, neurohumoral and coagulation factors were diminished. There were significant relationships between BP levels and plasma BNP levels, nocturnal urinary adrenalines and ET1s. There were also significant relationships between night/day ratio of BP and plasma ET1 level. In conclusion the abnormal patterns of circadian BP rhythm were frequently observed during the acute phase of stroke. The cause of this abnormality may result from the diminished circadian rhythms of neurohumoral factors.
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PMID:Circadian variation of blood pressure and neurohumoral factors during the acute phase of stroke. 1184 63

Aldosterone breakthrough during ACE inhibitor therapy has been reported. This study investigates changes in plasma aldosterone concentration (PAC) and its mechanism and effects on target organ damage during long-term angiotensin II type 1 (AT1) receptor antagonist (AT1A) therapy in hypertensive rats. An AT1A (candesartan, 1 mg/kg per day PO) was administered in stroke-prone spontaneously hypertensive rats from 4 weeks of age for 34 weeks. PAC was significantly decreased during the first 4 weeks but showed aldosterone breakthrough after 8 weeks of AT1A administration. Plasma angiotensin II concentration was significantly elevated, whereas no change was seen in plasma ACTH or serum potassium. The mechanism(s) of aldosterone breakthrough were investigated by giving high doses of candesartan (3 mg/kg per day PO), dexamethasone (200 microg/kg per day IP), or the AT2 antagonist (PD123319, 10 mg/kg per day SC) during the last week of the 24-week AT1A treatment period. Dexamethasone and AT2 antagonist but not high-dose AT1A produced a significant decrease in PAC, with a larger decrease produced by the AT2 antagonist. To clarify the effects of the residual aldosterone, effects of coadministration of low-dose spironolactone (10 mg/kg per day SC), an aldosterone antagonist, on left ventricular hypertrophy and expression of brain natriuretic peptide mRNA were determined. Low-dose spironolactone further improved left ventricular hypertrophy and brain natriuretic peptide mRNA expression despite no additional depressor effect. These results suggest that aldosterone breakthrough occurs during long-term AT1A therapy, mainly by an AT2-dependent mechanism. Residual aldosterone may attenuate the cardioprotective effects of AT1A.
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PMID:Aldosterone breakthrough during angiotensin II receptor antagonist therapy in stroke-prone spontaneously hypertensive rats. 1210 34

Imidapril hydrochloride (imidapril) is a long-acting, non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, which has been used clinically in the treatment of hypertension, chronic congestive heart failure (CHF), acute myocardial infarction (AMI), and diabetic nephropathy. It has the unique advantage over other ACE inhibitors in causing a lower incidence of dry cough. After oral administration, imidapril is rapidly converted in the liver to its active metabolite imidaprilat. The plasma levels of imidaprilat gradually increase in proportion to the dose, and decline slowly. The time to reach the maximum plasma concentration (T(max)) is 2.0 h for imidapril and 9.3 h for imidaprilat. The elimination half-lives (t(1/2)) of imidapril and imidaprilat is 1.7 and 14.8 h, respectively. Imidapril and its metabolites are excreted chiefly in the urine. As an ACE inhibitor, imidaprilat is as potent as enalaprilat, an active metabolite of enalapril, and about twice as potent as captopril. In patients with hypertension, blood pressure was still decreased at 24 h after imidapril administration. The antihypertensive effect of imidapril was dose-dependent. The maximal reduction of blood pressure and plasma ACE was achieved with imidapril, 10 mg once daily, and the additional effect was not prominent with higher doses. When administered to patients with AMI, imidapril improved left ventricular ejection fraction and reduced plasma brain natriuretic peptide (BNP) levels. In patients with mild-to-moderate CHF [New York Heart Association (NYHA) functional class II-III], imidapril increased exercise time and physical working capacity and decreased plasma atrial natriuretic peptide (ANP) and BNP levels in a dose-related manner. In patients with diabetic nephropathy, imidapril decreased urinary albumin excretion. Interestingly, imidapril improved asymptomatic dysphagia in patients with a history of stroke. In the same patients it increased serum substance P levels, while the angiotensin II receptor antagonist losartan was ineffective. These studies indicate that imidapril is a versatile ACE inhibitor. In addition to its effectiveness in the treatment of hypertension, CHF, and AMI, imidapril has beneficial effects in the treatment of diabetic nephropathy and asymptomatic dysphagia. Good tissue penetration and inhibition of tissue ACE by imidapril contributes to its effectiveness in preventing cardiovascular complications of hypertension. The major advantages of imidapril are its activity in the treatment of various cardiovascular diseases and lower incidence of cough compared with some of the older ACE inhibitors.
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PMID:Protection of the cardiovascular system by imidapril, a versatile angiotensin-converting enzyme inhibitor. 1217 88

Atrial natriuretic peptides (ANPs) consist of a family of peptides (atrial natriuretic factor [ANF], long acting natriuretic peptide, vessel dilator, kaliuretic peptide, urodilatin, brain natriuretic peptide [BNP], and C type natriuretic peptide [CNP]) which are synthesized within the heart, except for urodilatin. Of these natriuretic peptides, the vessel dilator radioimmunoassay (RIA) of a single plasma sample is the most sensitive and specific in the diagnosis of early (i.e., NYHA class I) congestive heart failure (CHF). Vessel dilator is beneficial in the treatment of CHF, enhancing of urine flow two- to 13-fold and sodium excretion three- to four-fold for 3 hours after stopping its infusion. This 37 amino acid peptide hormone simultaneously decreases systemic vascular resistance 24%, pulmonary vascular resistance 25%, pulmonary capillary wedge pressure 33%, and central venous pressure 27% while increasing cardiac output 34%, cardiac index 35%, and stroke volume index 24% in individuals with CHF. (c)1999 by CHF, Inc.
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PMID:Atrial natriuretic peptides in the diagnosis and treatment of congestive heart failure. 1218 9

Nesiritide, a recombinant human B-type natriuretic peptide, is the first in a new drug class for the treatment of decompensated heart failure. The drug binds to receptors in the vasculature, kidney, adrenal gland, and brain, and overcomes resistance to endogenous BNP present in patients with CHF. Nesiritide administration leads to a rapid and balanced vasodilatory effect, which results in a significant decrease in right and left ventricular filling pressures and systemic vascular resistance and at the same time in an increase in stroke volume and cardiac output without a change in heart rate. These early hemodynamic changes result in a rapid improvement in symptoms of heart failure. In addition, nesiritide lowers aldosterone, catecholamines, and endothelin-1 levels and its effect on the kidney leads to an increased natriuresis and diuresis without effect on serum potassium or renal function. Prior to its approval for clinical use, nesiritide was studied in 10 different clinical trials involving 941 patients with moderate and severe CHF, including elderly patients, patients with both systolic and diastolic dysfunction, and patients with arrhythmias, renal insufficiency, and acute ischemic syndrome. In comparative studies with available vasoactive therapies frequently used for treatment of patients with decompensated heart failure, nesiritide was proven comparable in efficacy to inotropic drugs such as dobutamine, but superior in safety. In a recent study, nesiritide was found to be more effective and better tolerated than the vasodilator, nitroglycerin. The most common side effects expected with the use of nesiritide are headaches and decrease in blood pressure. At the recommended dose of nesiritide, headache was reported during the first 24 hours of treatment in 8% of patients and symptomatic hypotension in 4% of patients, compared to 20% and 5% in nitroglycerin-treated patients.
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PMID:Nesiritide: a new drug for the treatment of decompensated heart failure. 1223 67

Recent studies have suggested a differential influence of mean pressure and pulse pressure on myocardial infarction and stroke, and differences among the major drugs in their efficacy at preventing these individual endpoints. We hypothesized that antihypertensive drugs have differing influences upon the pulse wave even when their effects on blood pressure are the same. We studied 30 untreated hypertensive patients, aged 28-55 years, who were rotated through six 6-week periods of daily treatment with amlodipine 5 mg, doxazosin 4 mg, lisinopril 10 mg, bisoprolol 5 mg, bendrofluazide 2.5 mg or placebo. The best drug was repeated at the end of the rotation. Blood pressure readings and radial pulse tonometry (by Sphygmocor) were performed at each visit, and blood was taken for measurement of levels of atrial natriuretic peptide and brain natriuretic peptide (BNP). The Sphygmocor derivation of the central aortic pulse wave was used to measure time for transmission of the reflected wave (T(R)) and the augmentation index (AI), which is the proportional increase in systolic pressure due to the reflected wave. There was a dissociation between the effects of the drugs on blood pressure and pulse wave analysis. Bisoprolol caused the greatest falls in blood pressure and T(R), but was the only drug to increase AI. This paradoxical response to bisoprolol was associated with a 3-fold increase in plasma BNP levels. There was a smaller elevation of BNP in women compared with men, as described previously, and this elevation also was associated with significantly higher values of AI. Other drugs reduced AI, and this was associated with a significant decrease in BNP by amlodipine. In conclusion, antihypertensive drugs differ in their short-term effects on augmentation of the systolic pulse wave and secretion of BNP from the heart, regarded as a sensitive measure of strain on cardiomyocytes. These differences may help to explain cause-specific differences in outcome in recent trials.
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PMID:Influence of drugs and gender on the arterial pulse wave and natriuretic peptide secretion in untreated patients with essential hypertension. 1240 Nov 23

Pulmonary hypertension is characterised by the chronic elevation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) leading to right ventricular enlargement and hypertrophy. Pulmonary hypertension may result from respiratory and cardiac diseases, the most severe forms occurring in thromboembolic and primary pulmonary hypertension. Pulmonary hypertension is most often defined as a mean PAP >25 mmHg at rest or >30 mmHg during exercise, the pressure being measured invasively with a pulmonary artery catheter. Doppler echocardiography allows serial, noninvasive follow-up of PAPs and right heart function. When the adaptive mechanisms of right ventricular dilatation and hypertrophy cannot compensate for the haemodynamic burden, right heart failure occurs and is associated with poor prognosis. The haemodynamic profile is the major determinant of prognosis. In both primary and secondary pulmonary hypertension, special attention must be paid to the assessment of pulmonary vascular resistance index (PVRI), right heart function and pulmonary vasodilatory reserve. Recent studies have stressed the prognostic values of exercise capacity (6-min walk test), right atrial pressure, stroke index and vasodilator challenge responses, as well as an interest in new imaging techniques and natriuretic peptide determinations. Overall, careful haemodynamic evaluation may optimise new diagnostic and therapeutic strategies in pulmonary hypertension.
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PMID:Haemodynamic evaluation of pulmonary hypertension. 1244 89


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