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

Percutaneous transluminal angioplasty (PTA) was used to treat 66 patients with 85 renal artery stenoses due to fibromuscular dysplasia. The hypertension was refractory to medical management in 46 patients, and the initial success rate was 100%. Clinical follow-up has been obtained in all patients, who were followed for as long as 121 months. The recurrence rates were 8% of lesions and 10% of patients. Cumulative patency rate predicted for 10 years was 87.07%. The mean systolic pressure decreased by 52 mm Hg and the mean diastolic pressure decreased by 35 mm Hg in response to treatment. Twenty-six patients (39%) were cured, 39 (59%) were classified as improved, and one (2%) did not respond to PTA. Fourteen of the patients also had elevated blood urea nitrogen and creatinine levels. Renal function was improved in 86% of the patients and stabilized in 14% of the patients. Analysis of the long-term results suggests that PTA should be the initial treatment for choice of patients with fibromuscular dysplasia in the renal arteries.
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PMID:Results and complications of angioplasty in fibromuscular disease. 182 43

We measured plasma concentrations of immunoreactive endothelin-1 (irET-1) in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in malignant hypertension caused by deoxycorticosterone acetate (DOCA)-salt administration in SHR. We also measured concentrations of this peptide in another model of malignant hypertension, the two-kidney, one clip (2K1C) renovascular hypertensive rats chronically given caffeine. Plasma irET-1 concentrations in young (6-week-old) and mature (18-week-old) SHR did not differ from those of age-matched Wistar-Kyoto (WKY) rats. Four weeks of treatment with DOCA-salt increased blood pressure, blood urea nitrogen, serum creatinine, and plasma irET-1 in SHR but not in WKY rats. Eight weeks of DOCA-salt treatment further increased these values in SHR. Plasma irET-1 concentrations were not increased in the 2K1C rats. Six weeks of caffeine administration increased blood pressure, blood urea nitrogen, serum creatinine, plasma renin activity, and plasma irET-1 in the 2K1C rats but not in the sham-operated rats. High-performance liquid chromatographic profiles of plasma extracts pooled from these rats with malignant hypertension showed that a major component of irET-1 eluted in the position of synthetic ET-1 (1-21). Furthermore, acute hypertension induced by angiotensin II or phenylephrine did not affect the plasma irET-1 concentration in rats. The results suggested that the plasma ET-1 concentration is increased in rat models of malignant hypertension and that the high blood pressure itself is not the main factor involved in the increase of plasma ET-1.
Hypertension 1991 Jul
PMID:Plasma immunoreactive endothelin-1 in experimental malignant hypertension. 186 Jul 18

The long-term results of pediatric heart transplantation were evaluated in 53 patients, aged 0.25 to 18.94 years, who received transplants at Stanford University Medical Center between 1974 and 1989. Indications for transplantation were idiopathic cardiomyopathy (68%), congenital heart disease (21%), endocardial fibroelastosis (8%), and doxorubicin cardiomyopathy (3%). Immunosuppression was achieved with combinations of cyclosporine, prednisone, and azathioprine. Thirty-seven of 42 recipients leaving the hospital after transplantation were alive and in New York Heart Association class I at study's end. Cumulative survival was 79% at 1 year, 76% at 3 years, and 69% at 5 years. Fourteen recipients have survived more than 5 years (5.1 to 12.4 years). Hospital readmission for illness has been infrequent, decreasing from 6.8 days to 0.9 days per year over 5 years. Eleven patients have required no rehospitalization. Posttransplant deaths were due to infection (19%), rejection (4%), pulmonary hypertension (4%), coronary artery disease (2%), and lymphoproliferative disease (2%). Retransplantation was required for intractable rejection in 4 patients and advanced coronary artery disease in 2. Hypertension and elevated blood urea nitrogen and creatinine levels were common in individuals receiving cyclosporine. Growth was often impaired in prepubertal children receiving daily prednisone. Based on this 15-year experience, it is concluded that heart transplantation represents a reasonable alternative for selected young patients with end-stage cardiac disease.
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PMID:Pediatric heart transplantation at Stanford: results of a 15-year experience. 186 16

Percutaneous transluminal renal angioplasty was performed in a 63-year-old diabetic woman who had renovascular hypertension with solitary functioning kidney and diffuse atherosclerosis. Angioplasty was technically successful, while thereafter, fever and myalgia of legs occurred with gradual increases in blood urea nitrogen and creatinine. The patient became uremic over a month after angioplasty and was placed on dialysis. She died six months after angioplasty. Autopsy revealed cholesterol embolization in bilateral kidney, pancreas and spleen, causing subacute renal failure. It is suggested that careful assessment of the patient should be made when determining the need for renal angioplasty for renovascular hypertension with a solitary functioning kidney.
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PMID:Renal failure due to cholesterol embolization following percutaneous transluminal renal angioplasty. 186 75

EDRF is a potent, endogenous vasodilator that is produced and released from endothelial cells and subsequently causes the relaxation of VSM through the activation of soluble guanylate cyclase and an increase in VSM cyclic GMP. Structurally, EDRF is likely to be NO or a related nitrogen oxide-containing compound. It is synthesized in endothelial and other cell types from L-arginine by a calcium-calmodulin and NADPH-dependent enzyme. Its action is very similar to the nitrovasodilators that act directly on VSM. EDRF is present in all vascular beds, large and small vessels, and in a wide range of species. Its role in human vascular physiology and pathophysiology is just beginning to be understood. EDRF is a potent endogenous vasodilator and inhibitor of platelet aggregation and adhesion. Its activity is impaired in hypertension and atherosclerosis, and its absence due to endothelial damage may play a role in cerebral and coronary vasospasm. It is a mediator of flow-dependent vasodilation, and its inhibition by hypoxia may contribute to the hypoxic pulmonary vasoconstrictor response. Endothelial cell damage and impairment of EDRF production may also contribute to acute and chronic pulmonary hypertension. A further understanding of the chemical nature and synthetic pathways of EDRF should lead to the production of analogs and antagonists, which may play an important role in future treatments for atherosclerosis, myocardial infarction, angina, hypertension, and other vascular diseases. The recent realization that EDRF serves as the second messenger for guanylate cyclase activation and cyclic GMP production in a variety of cell types outside of the cardiovascular system, including renal and respiratory epithelium, cerebellar neurons, macrophages, and adrenocytes, suggests even broader implications. The importance of EDRF to the anesthesiologist may go beyond an understanding of its role in cardiovascular physiological and pathophysiological states. Initial studies have shown that the endothelium may play a role in mediating the vascular actions of anesthetics, and that anesthetics can inhibit the production, release, or action of EDRF. How are these interactions mediated? Are there significant differences between anesthetics with regard to their effects on EDRF? Is there a clinically significant effect of anesthetics on basal activity of EDRF, or only in response to exogenous stimulation? Conversely, it is important to determine if alterations in endothelial cell function by various disease states such as hypertension, atherosclerosis, adult respiratory distress syndrome, cerebral vasospasm, and others cause changes in the vascular actions of anesthetics. The potential interactions of anesthetics with EDRF production and action in cell types other than the endothelium have not yet been explored.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endothelium-derived relaxing factor: basic review and clinical implications. 186 89

We analyzed the records of all residents of Jefferson County, Alabama, accepted for renal replacement therapy between 1982 and 1987 and compared them with those accepted between 1974 and 1978 to determine any changes in the distribution and frequency of end-stage renal disease (ESRD) due to hypertension (H-ESRD). H-ESRD increased from 6.4 to 9.6 per 100,000 in blacks and from 0.36 to 0.62 per 100,000 in whites. Smoothed age- and race-specific yearly H-ESRD rates decreased in blacks under age 50. Peak incidence of H-ESRD shifted from age 40 to 49 in 1974 through 1978 to age 50 to 59 in 1982 through 1987 (P less than 0.0001). Blacks were referred for care with significantly higher blood pressure levels and serum creatinine concentrations than whites, and had more severe retinal vascular disease. Factors significantly associated with a shorter time from referral to renal replacement therapy were black race, female gender, blood urea nitrogen and serum creatinine concentrations, carbohydrate intolerance, and the use of alpha-agonist and/or angiotensin-converting enzyme (ACE) inhibitor. We conclude that racial distribution and risk for H-ESRD have not changed. Peak rates of H-ESRD have been delayed nearly a decade, suggesting a possible effect of better awareness and treatment of hypertension.
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PMID:Changing patterns of end-stage renal disease due to hypertension. 188 25

Serotonin (5-HT) is a potent bioactive substance known to function through a number of different receptor types and subtypes. In our attempt to develop new agents that would interact selectively at certain 5-HT receptors, especially the 5-HT1A subtype, 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT) served as a template for the design of novel agents sharing aspects of the pharmacophore of 8-OH-DPAT and 5-HT. 5-HT contains no center of asymmetry, and 8-OH-DPAT shows only very modest stereospecificity for 5-HT1A receptors. To develop agents having enhanced potency and selectivity for the 5-HT1A site, several ring systems offering enhanced conformational rigidity which approximate the oxygen to nitrogen interatomic distances of 8-OH-DPAT and (to a lesser extent) 5-HT were synthesized. Exemplary ring systems include the 8-alkoxy-hexahydroindeno[1,2-c]pyrrole, 5-alkoxy-hexahydro-1H-indeno-[2,1-c]pyridine, and 9-alkoxy-hexahydro-1H-benz[e]isoindole systems. These conformationally restricted molecules demonstrated moderate stereospecificity in their interaction with the 5-HT1A binding site, which was enhanced in compounds with larger nitrogen substituents. Appropriate choice of such derivatives led to highly potent compounds selective for 5-HT1A sites compared with their activity at other 5-HT and/or adrenergic receptors. The pharmacological profile of compounds which appear to act as agonists at 5-HT1A receptors in the central nervous system to lower blood pressure in animal models of hypertension is presented.
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PMID:Molecular design of novel ligands for 5-HT1A receptors. 188 79

Calcium channel antagonists are commonly used to treat chronic hypertension. Several studies of intact vascular tissues suggest that these agents may impair the production of the endothelium-derived relaxing factor and alter endothelium-dependent vascular relaxation. These studies are difficult to interpret because the calcium channel antagonist may have direct effects on vascular smooth muscle. In our study, a chemiluminescence assay was used to measure the release of nitrogen oxides from bovine aortic endothelial cells (BAEC) grown in monolayer. Under basal conditions, the release of nitrogen oxides was 0.2 nmol/100 mg protein and was increased approximately two-fold by 0.1 micrograms, bradykinin. Incubations with diltiazem, verapamil, and nifedipine for 60 min did not influence the basal and bradykinin-stimulated release of nitrogen oxides by BAEC. These data illustrate that the production of the endothelium-derived relaxing factor is not altered by the calcium channel antagonist, and are compatible with an absence of L-type calcium channels in vascular endothelial cells. Chronic hypertension produces myriad adverse effects in the coronary circulation. After coronary occlusion, infarct size, expressed as a function of myocardial mass perfused, is increased by 33%, and the wavefront of infarction from subendocardium to subepicardium is hastened. Both chronic and acute hypertension produce numerous abnormalities of coronary flow regulation. These include impairments of autoregulation, changes in vascular responsiveness, and alterations of endothelial cell function. Many of these may worsen the clinical consequences of ischemic heart disease, either by producing structural alterations of the coronary vasculature, or equally importantly, by altering coronary vascular responsiveness to either mechanical or neurohumoral stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypertension and the coronary circulation. With special attention to endothelial regulation. 191 Jun 38

Effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on blood pressure and hypertensive complications in stroke-prone spontaneously hypertensive rats (SHRSP) were investigated. Betaxolol was provided in a dose of 33 +/- 1.8 mg/kg/day, orally in drinking water, throughout the experimental period. The chronic treatment with betaxolol inhibited the development of hypertension in SHRSP and reduced values of blood urea nitrogen, creatinine, total cholesterol, free cholesterol, triglyceride, phospholipid and HDL-cholesterol in serum. Treatment with betaxolol apparently inhibited the incidence of hypertensive lesions such as cardiac fibrosis, mesenteric vasculitis, proliferative and/or necrotic vasculitis and glomeruli showing collapse or vasculitis in the kidneys. To shorten the time before the onset of hypertension and the subsequent stroke, SHRSP were kept on a SP diet containing 0.39% Na instead of the F-2 diet. When the SHRSP were kept on the SP diet, all of the control SHRSP had cerebral apoplexy and severe hypertensive lesions in the heart and kidney. When betaxolol was chronically administered to SHRSP, cerebral apoplexy and hypertensive lesions in the heart and kidney were inhibited, but the effect on blood pressure was slight. Treatment with betaxolol reduced serum creatinine levels. Our observations show that betaxolol reduces blood pressure and potently inhibits hypertensive complications in SHRSP.
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PMID:[Antihypertensive effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, in stroke-prone spontaneously hypertensive rats (SHRSP)]. 197 70

Plasma atrial natriuretic peptide (ANP) levels were measured in non-dialyzed and dialyzed chronic renal failure (CRF) patients and in normal subjects. Changes in plasma ANP in response to hemodialysis (HD) and to isolated ultrafiltration (UF) were also investigated in dialyzed CRF patients. Plasma ANP levels were significantly higher in 28 non-dialyzed CRF patients than in 27 normal subjects (mean +/- SEM, 174.0 +/- 25.9 vs 25.0 +/- 1.9 pg/ml, p less than 0.001). Plasma ANP levels did not correlate with blood urea nitrogen or serum creatinine, however patients with advanced renal failure (creatinine clearance less than 10 ml/min) with cardiomegaly (cardiothoracic ratio greater than 50%) or hypertension (BP greater than 140/90 mmHg) had significantly higher plasma ANP levels than those who were not. A 6-hour HD significantly decreased the plasma ANP level (423.4 +/- 71.3 to 220.6 +/- 40.0 pg/ml, p less than 0.001) and body weight in 21 dialyzed CRF patients, and the decrement in plasma ANP showed a positive correlation with the decrement in body weight (r = 0.425, p = 0.056). In 8 dialyzed CRF patients, we further performed a 1-hour isolated UF for removal of isoosmotic intravascular fluid without changes in the solute concentrations, followed by a subsequent 5-hour HD. The decrease in plasma ANP during the 1-hour UF period was 68% of the total ANP decrement for the whole 6-hour study. The average plasma ANP level was decreased with 94.6 +/- 42.5 pg/ml/kg/h in the UF period compared to 3.5 +/- 1.4 pg/ml/kg/h in the HD period (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma atrial natriuretic peptide in patients with chronic renal failure. 198 Dec 24


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