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:C0085580 (essential hypertension)
14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibitors of the angiotensin conversion enzyme (ICE) represent an effective and well tolerated therapeutic class, for the treatment of arterial hypertension. The antihypertensive efficacy or perindopril, an ICE active in one single daily dose, is at least equal to that of reference antihypertensive drugs administered at usual doses. The possibility of occurrence of some side-effects while using ICE, has resulted in a particular attention in evaluating the safety of perindopril. First, the renal function was monitored. During essential hypertension, no significant variation of the creatininemia was observed with long-term administration of the drug (12 months). In elderly hypertensive patients or patients with chronic renal insufficiency, the glomerular filtration is also preserved, except during rare occurrences of decreased creatinine clearance, especially after adjunction of hydrochlorothiazide. A discrete elevation of the kaliemia without clinical significance is observed when perindopril is used as a single drug. Reports of symptomatic hypotension with perindopril are rare (0.2%), even in situations of water and sodium depletion. Among other side-effects of ICE, cough, more recent, was thoroughly investigated. Its frequency was determined during a double blind trial comparing perindopril (1.2%) with captopril (2.4%). It was also evaluated during a long-term study concerning 632 hypertensive patients (391 patients treated in 1 year); its incidence is the 2.9 p. cent and it resulted in discontinuation of the treatment in 8 cases. In this study, 36 patients interrupted the treatment prematurily because of an adverse reaction (5.7%). Finally no harmful drug interaction was reported. The favorable tolerance profile of perindopril is combined with a beneficial effect on the functional and structural modifications of the heart and large vessels related to hypertension.
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PMID:[First intention treatment of arterial hypertension. Effectiveness and safety of perindopril]. 268 25

Renin plays a major role in the control of blood pressure and water and electrolyte metabolism and it is clear that blocking of this system is particularly effective in the treatment of essential hypertension and heart failure. A large number of converting enzyme inhibitors have been synthesized. Converting enzyme inhibitors are remarkably active in heart failure and they reduce microalbuminuria and possibly maintain glomerular function. Blocking of the renin-angiotensin system by converting enzyme inhibitors is not accompanied by hypotension or reflex stimulation of the sympathetic nervous system. Converting enzyme inhibitors represent a major therapeutic advance in the field of cardiovascular and renal disease but the long-term effects of decreased angiotensin II levels are unknown. There are other ways to inhibit the renin-angiotensin system. The recent discovery of orally-active non-peptide angiotensin II antagonists opens a range of fascinating prospects. Another approach consists in inhibiting the reaction of renin on angiotensinogen, which is remarkably selective. Although it is too early to know whether these new approaches will be less active, more active or as active as current converting enzyme inhibitors, they may constitute a progress in relation to currently available treatments.
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PMID:New therapeutic prospects of renin-angiotensin system inhibition. 269 Nov 25

The antihypertensive efficacy and effects on body fluid composition of monotherapy with the calcium antagonist nifedipine were investigated in 15 patients with essential hypertension. The systolic as well as the diastolic blood pressure decreased significantly, by approximately 12%, during nifedipine treatment with a mean dose of 56 mg. Glomerular filtration rate, plasma volume, extracellular fluid volume, and the ratio plasma to interstitial fluid volume did not change significantly. The most frequently observed side-effects were flushing and peripheral oedema which occurred in four and three patients, respectively. These results indicate that sodium and water retention, which is often observed during long-term treatment with vasodilators, does not seem to be the explanation of the development of peripheral oedema seen with nifedipine.
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PMID:Effect of long-term nifedipine treatment on body fluid composition in essential hypertension. 276 76

During chronic chlorthalidone treatment of patients with essential hypertension, distal tubular sodium reabsorption is continuously inhibited. At the same time, sodium balance is maintained by an increase of the proximal tubular sodium reabsorption. In the present study, we investigated whether this increase is caused by a stimulated renin-angiotensin system (RAS). For this purpose, the renal effects of converting enzyme inhibition (CEI) were evaluated in 12 patients with essential hypertension who remained hypertensive despite chronic chlorthalidone treatment. After 6 weeks of chlorthalidone, an intravenous injection of 10 mg enalaprilic acid decreased the mean arterial pressure (MAP) from 110 to 102 mm Hg. The effective renal plasma flow (ERPF) increased. However, glomerular filtration rate (GFR) and the fractional excretions of sodium, lithium and free water did not change significantly. After 2 additional weeks of chlorthalidone combined with enalapril 20 mg b.i.d., MAP fell to 90 mm Hg, ERPF remained elevated and plasma aldosterone concentration decreased. As in the acute study, no significant changes were detected in the GFR and the fractional excretions of sodium, lithium or free water. Extracellular fluid volume was not diminished during these 2 weeks. Fractional proximal sodium reabsorption during chronic chlorthalidone therapy was higher when calculated from free water clearance (91%) than from the lithium clearance (71%), but neither of the two were affected by acute or chronic CEI. The results of this study suggest that during chronic diuretic treatment, maintenance of sodium balance by increased proximal reabsorption is not dependent on the stimulated RAS, or alternatively, that this function of the RAS is exactly counterbalanced by another effect of CEI, possibly by the fall in blood pressure.
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PMID:The effect of converting enzyme inhibition on the enhanced proximal sodium reabsorption induced by chronic diuretic treatment in patients with essential hypertension. 282 50

The acute hypotensive and renal effects of the calcium antagonist tiapamil, a verapamil derivative, were studied in nine normal and 13 essential hypertensive subjects undergoing water diuresis. Tiapamil decreased mean arterial pressure slightly in normotensive subjects and more markedly in hypertensive patients (-6 +/- 1 versus -10 +/- 2%). The effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were unaffected in both groups. A striking natriuresis was observed selectively in the hypertensive group (+344 +/- 84 versus +42 +/- 22 mmol/min) and was associated with an increase in the calculated fractional distal delivery of sodium and uric acid excretion rate. Plasma aldosterone concentration decreased moderately and to the same extent in both groups. In conclusion, tiapamil induced a marked natriuresis in essential hypertensive patients, despite a decrease in blood pressure, and in the absence of renal vasodilatation; this may suggest the existence in essential hypertension of a calcium-linked abnormality in the renal proximal tubular handling of sodium.
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PMID:Renal effects of calcium blockade by tiapamil in normal and hypertensive subjects. 285 96

The widespread prevalence of hypertension in the United States and the enormous expense and effort associated with its treatment necessitate a cost-conscious approach to evaluation and therapy. In the past, we have devoted too many resources to testing for rare diseases suspected of causing hypertension when it has been demonstrated that secondary causes are rare. Devoting resources to the effective treatment of essential hypertension itself should be a priority, because such treatment has been shown to reduce morbidity and mortality associated with hypertension and related cardiovascular diseases. Clinical and epidemiologic studies have demonstrated that treatment for hypertension should not be initiated unless diastolic blood pressure readings are 90 mm Hg or greater on three successive office visits. Treatment should be carried out in a step-wise fashion, using a non-pharmacologic approach only in situations in which hypertension is mild, target organ disease is absent, and compliance is favorable. Diuretics should be used as step-one drug therapy in most situations, because they are effective in the majority of patients, convenient to use, easy to titrate, and comparatively inexpensive. They do not cause salt and water retention, and side effects are usually minimal. When the use of diuretics is contraindicated, beta blockers are suitable alternatives, equally effective in most respects. When beta blockers or other non-diuretic drugs are used as step-one therapy and an additional drug is needed, diuretics can be used advantageously in conjunction with the step-one drug.
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PMID:Essential hypertension: cost-effective evaluation and treatment. 287 55

Whether the dopaminergic system may be involved in essential hypertension is of pathogenetic as well as therapeutic interest. Therefore, we investigated in eight hypertensive and 12 normal subjects cardiovascular, endocrine, and renal responses to fenoldopam, which has been characterized experimentally as an agonist of peripheral postsynaptic dopamine1 receptors. A single oral dose of fenoldopam, 100 mg, changed blood pressure (BP) in hypertensive subjects (from 163/103 to 147/76 mm Hg; p less than 0.01 for systolic and p less than 0.001 for diastolic BP) and normal subjects (from 121/81 to 123/65 mm Hg; p less than 0.001 for diastolic BP); percentage decreases in diastolic BP averaged -20 +/- 6 and -16 +/- 7%, respectively. Fenoldopam-induced effects on other variables were similar in the two groups. Heart rate rose (p less than 0.001) on average from 69 to 92 beats/min in hypertensive and from 64 to 84 beats/min in normal subjects. Effective renal plasma flow increased (from 552 to 765 and 634 to 937 ml/min/1.73 m2; p less than 0.01), while glomerular filtration rate tended to decrease (from 121 to 99 ml/min/1.73 m2 in the hypertensive and from 119 to 97 ml/min/1.73 m2; p less than 0.001 in the normal group). Fractional sodium clearance was elevated (from 2.8 to 5.2 and 1.7 to 3.8%; p less than 0.01), as was free water clearance (from -1.7 to 0.6 and -1.7 to 0.1 ml/min/1.73 m2; p less than 0.01). Potassium clearance was largely unchanged. Plasma renin activity increased about twofold (p less than 0.01 in normal subjects), and plasma aldosterone by 40% (NS). Plasma norepinephrine levels increased twofold to 2.5-fold (p less than 0.001), and urinary norepinephrine excretion fivefold to 10-fold (p less than 0.01). Fenoldopam-induced changes were not significantly modified by intravenous and/or oral pretreatment with the dopamine-receptor antagonist metoclopramide or the cyclooxygenase inhibitor indomethacin. These findings suggest that in humans, fenoldopam may acutely override the dopaminergic antagonism of metoclopramide given in clinical dosage and that its cardiovascular and renal effects are not prostaglandin-mediated. Although acute sympathetic stimulation may be partially antagonistic, the concomitant BP-lowering, renal vasodilating, and natriuretic actions of fenoldopam represent a desirable profile of a potential antihypertensive agent.
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PMID:Cardiovascular and renal profile of acute peripheral dopamine1-receptor agonism with fenoldopam. 288 68

Activation of dopamine1 (DA1) receptors relaxes vascular smooth muscle, especially in the renal vascular bed. Fenoldopam, the first selective DA1-receptor agonist that can be administered to man, was infused intravenously in 17 patients with essential hypertension (mean blood pressure 152/101 mm Hg). It reduced blood pressure in a dose-dependent fashion at doses between 0.025 and 0.5 microgram/kg/min and the antihypertensive effect was sustained during 2 hr infusions. In 10 patients studied during free-water diuresis, fenoldopam increased renal plasma flow by 42%, glomerular filtration rate by 6%, and sodium excretion by 202%, while lowering mean arterial pressure by 12% (all p less than .05). Similar promotion of sodium excretion was observed during blood pressure reduction in six additional patients studied without water loading. Pronounced enhancement of renal function in spite of blood pressure reduction suggests that fenoldopam might have a special role in the treatment of patients with hypertension and renal impairment.
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PMID:Augmentation of renal blood flow and sodium excretion in hypertensive patients during blood pressure reduction by intravenous administration of the dopamine1 agonist fenoldopam. 289 Apr 47

Plasma concentrations of human atrial natriuretic peptide (hANP) and effects of synthetic alpha-hANP on blood pressure (BP), on endocrine and metabolic variables, and on renal function were investigated in 10 patients with essential hypertension. Alpha-human atrial natriuretic peptide was given intravenously as a 50-micrograms bolus followed by a 45-min infusion at 0.1 microgram/kg per min. The following effects were observed: (1) a marked rise in plasma alpha-hANP, (2) a progressive fall in BP (from 181/127 to 165/109 mmHg) and plasma volume, (3) a probably baroreflex-mediated sympathetic activation, evidenced by raised heart rate and plasma norepinephrine levels, (4) an increase in serum free fatty acids and circulating insulin (+45%), (5) an enhanced diuresis (+770%) and excretion of sodium (+665%), chloride (+524%), phosphate (+518%), other electrolytes, amino acids and free water clearance, (6) biphasic responses in the glomerular filtration rate (GFR) and p-aminohippurate (PAH) clearance, with initial increases (+40 and 30%, respectively) followed by a rapid return to (GFR), or even a fall below (PAH clearance) control values, and (7) a marked rise in the filtration fraction. Plasma antidiuretic hormone and urinary prostaglandin E2, F2 alpha and dopamine levels were not modified during alpha-hANP infusion, while plasma renin increased. Discontinuation of alpha-hANP was followed by rises in plasma aldosterone, the aldosterone:renin ratio and cortisol. Compared with previously studied normal subjects, in the hypertensive patients alpha-hANP caused a distinctly greater diuresis and electrolyte excretion but lowered BP only slightly more. In essential hypertension, as in normal man, alpha-hANP circulates in the blood and may exert a wide spectrum of cardiovascular, metabolic, endocrine and renal actions.
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PMID:Cardiovascular, endocrine and renal effects of atrial natriuretic peptide in essential hypertension. 294 46

A sensitive and specific radioimmunoassay for alpha-human atrial natriuretic polypeptide (alpha-hANP) was developed to determine its plasma level. Anti-alpha-hANP rabbit serum was specific for the N-terminus and ring structure of alpha-hANP, and showed no appreciable cross-reactions with other neuropeptides. The lowest level of alpha-hANP detectable by this radioimmunoassay was 4 pg per tube. The intra- and inter-assay coefficients of variation were 4.6-11.4% and 7.9-11.8%, respectively, and the recovery rates at 4 concentrations were 62.6-74.0%. The fasting plasma alpha-hANP concentration in normal subjects were 19.3 +/- 1.0 ng/l (mean +/- SE; n = 54), and there was no sex difference. The plasma alpha-hANP level in normal subjects fell significantly during water deprivation and increased significantly on infusion of hypertonic saline. The mean plasma levels of alpha-hANP were higher than normal in patients with essential hypertension, liver cirrhosis, congestive heart failure and chronic renal failure. Our results indicate that this radioimmunoassay is suitable for determining the alpha-hANP concentration in human plasma and can assess changes in pathological and physiological states.
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PMID:Radioimmunoassay for atrial natriuretic peptide: method and results in normal subjects and patients with various diseases. 294 73


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