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

The ultimate aim in treating hypertension is to reduce cardiovascular mortality and morbidity, especially from coronary heart disease and strokes. In several long-term trials this goal has been achieved with antihypertensive therapy in the form of diuretics. Subsequently, diuretics and betablockers, compared as single agents or with the addition of other agents, did not appear to affect overall cardiovascular morbidity and mortality differentially. Therefore, recommended first-line therapy for hypertension was initially diuretics, followed later by beta blockers as alternatives. Recently, calcium antagonists and ACE inhibitors have been accepted as equally valuable in the treatment of hypertension because they similarly lower blood pressure, lack any adverse metabolic effects and may be more beneficial than diuretics or beta-blockers on the long-term prognosis of hypertensive patients. Such recommendations are, however, highly speculative and are not supported by trials using cardiovascular mortality and morbidity as endpoints. In order to solve the conflict between proven facts and sound theory, long-term trials comparing older (mainly diuretics) and newer (calcium antagonists, ACE inhibitors, alpha-adrenoceptor blockers) antihypertensive agents are needed. Until such trials are completed, the debate surrounding first-line drugs for antihypertensive treatment will not be resolved.
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PMID:Where now the diuretics in antihypertensive treatment? 136 42

Echocardiographically determined left ventricular mass (LVM) is currently considered to be the most powerful risk indicator for cardiovascular disease, yielding prognostic information beyond that provided by the evaluation of traditional cardiovascular risk factors, high blood pressure included. It has been considered logical to try to obtain regression of cardiac hypertrophy, even though the risk-reducing implications of such a measure remain to be fully established. Experimental and clinical studies have shown that some classes of antihypertensive compounds are less effective than others in causing reversal of left ventricular hypertrophy (LVH) in spite of being similarly efficacious in lowering blood pressure. In order to extract the maximum amount of information from clinical studies, a meta-analysis was performed. This analysis included 109 treatment studies, each conformed to strict present rules. Only studies with pharmacological antihypertensive therapy and echocardiographically determined LVM were included. An analysis of the effect of the four first-hand antihypertensive treatment principles, adjusted for differences between studies with ANCOVA, showed that the ACE inhibitors, beta-blockers and calcium antagonists all reduce LVM by reversing wall hypertrophy and that the effect is most pronounced with ACE inhibitors. Diuretics reduce LVM mainly by a reduction in left ventricular diameter. If the difference in ability to reverse LVH, between ACE inhibitors and beta-blockers/diuretics would correspond to a difference in prognosis, then the outcome of antihypertensive therapy might be expected to improve. This hypothesis is currently under investigation.
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PMID:Regression of left ventricular hypertrophy--are there differences between antihypertensive agents? 136 88

Inhibitors of the angiotensin converting enzyme (ACE, EC 3.4.15.1) are important in the treatment of the high blood pressure. The therapeutically used drugs captopril, enalapril and ramipril are enzymatic stable short pseudo-peptides. They are stabilized against enzymatic degradation and therefore usefully for oral application. But for some indications e.g. post operative treatment and shock therapy well dosed infusions are needed. For this purpose we attached nona-, penta- and tripeptide inhibitors of the ACE to immunologically inert dextran polymers. The inhibitors are derived as well from the bradykinin potentiating nonapeptide BPP9 alpha (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) and the bradykinin potentiating pentapeptide BPP5 alpha (Pyr-Lys-Trp-Ala-Pro), both originally isolated from snake venoms, as from acylated tripeptides with the structure Acyl-AA1-Arg-Pro. We estimated the influence on the biological activity of two different linkers to the dextran polymers. The coupling to the polymer was achieved on the one hand via the aldehyd moiety (DAD-AK) and on the other hand by the carboxyl residue (KMD). In the case of DAD-AK-polymers the condensation of the peptides was performed by the N-hydroxysuccinimide ester of the polymer. Because of the instability of the KMD-OSU in this case water soluble carbodiimides are used. The polymer bound peptides inhibit the isolated ACE, but in the most cases with a reduced activity. Only the tripeptide DPhe-Arg-Pro has a enhanced activity in the polymer bound state. The polymer bound inhibitors show a prolongated action on normotensive rats by intravenous application.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Peptide inhibitors of the renin-angiotensin system. 2. Polymer-bound tri-, penta- and nonapeptide inhibitors of angiotensin converting enzyme]. 138 10

Felodipine is a vascular-selective, dihydropyridine calcium antagonist previously investigated as a conventional tablet formulation administered twice daily. More recently considerable experience has been gained with an extended release (ER) formulation which has the convenience of once daily administration. Felodipine ER has been well studied in patients with essential hypertension. As monotherapy in mild to moderate essential hypertension, felodipine ER is at least as effective in reducing blood pressure as other calcium antagonists, beta-blockers, diuretics and ACE inhibitors, with some results favouring felodipine ER at a statistically significant level at the dosages used. It is also effective combined with controlled release metoprolol or enalapril in patients with mild to moderate essential hypertension. In patients with more severe forms of essential hypertension uncontrolled by beta-blocker and/or diuretic therapy, felodipine ER was effective as an 'add-on' therapy in placebo-controlled trials, and, at the dosages used, more effective than either sustained release nifedipine or nitrendipine. Felodipine produces effective control of blood pressure without negative effects on cardiac performance. In addition to its antihypertensive action, results suggest that felodipine therapy is associated with significant regression of left ventricular hypertrophy. Furthermore, it appears suitable for use in patients with concomitant diabetes, renal dysfunction or asthma, and is also being investigated for use in patients with congestive heart failure or angina pectoris. Felodipine ER is an effective drug for the treatment of all grades of essential hypertension, and can be used both as monotherapy and in combination with other antihypertensive agents. Further clinical experience should fully establish the long term tolerability of felodipine ER and consequently its place in therapy relative to other accepted antihypertensive drugs. However, with the convenience of once daily administration, felodipine ER is a worthwhile innovation in the treatment of hypertension.
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PMID:Felodipine. A review of the pharmacology and therapeutic use of the extended release formulation in cardiovascular disorders. 138 18

Hypertension and diabetes mellitus are strongly associated conditions from epidemiologic, genetic, and pathophysiologic points of view. The prevalence of hypertension is high in patients with diabetes, and, conversely, many patients with essential hypertension are glucose intolerant. Proteinuria appears in 40-50% of patients with insulin-dependent diabetes mellitus and 20-30% of patients with non-insulin-dependent diabetes mellitus. Progressive renal failure occurs in 30-40 and 3-8% of patients, respectively, hypertension being a leading factor in its rate of progression. In various animal experiments, ACE inhibitors are able to prevent proteinuria and glomerular sclerosis, presumably by lowering transglomerular capillary pressure. In the diabetic human, ACE inhibitors are powerful antihypertensive drugs, devoid of metabolic side effects. Clinical studies indicate that ACE inhibitors reduce proteinuria and possibly slow the rate of decline in renal function. Such an effect is not observed with beta-blockers. Large-scale studies are needed to confirm this very important hypothesis.
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PMID:Angiotensin-converting enzyme inhibition and diabetic nephropathy. 138 63

First-dose-response of captopril 1 x 25 mg (no prodrug) and ramipril 1 x 2.5 mg (prodrug) were compared in two groups of 17 patients with moderate or severe hypertension and stimulated renin-angiotensin system (because of continuous diuretic therapy) by means of 24-h blood-pressure measurement at the 1st and 7th day of therapy. In the ramipril-group the antihypertensive effect started after 2 h, had its maximum (mean: -13/-8 mmHg) after 4 h and remained unchanged for 8 h. The antihypertensive effect was significant for 24 h. There was a slightly but not significant improved blood-pressure reduction at the 7th day compared to the 1st. The captopril-group showed a fast and marked decrease of blood pressure within the first hour, and reached its maximum (mean: -18/-10 mmHg) after 2 h. After 7 h there was no antihypertensive effect detectable. At the 7th day blood-pressure reduction was less pronounced compared to the 1st day. The results show that initial decrease of blood pressure in risk-patients is less severe with prodrug-ACE-inhibitors with slow onset of action so that counterregulation can be activated and prevent severe, fast, ACE-inhibitor-induced hypotension. 24-h-blood-pressure measurement is a sufficient method to evaluate first-dose-response of ACE-inhibitors.
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PMID:[Long-term blood pressure measurement for evaluating the first dose response of captopril and ramipril in patients with a stimulated renin system]. 138

Reduction of high blood pressure has an effect on coronary mortality and morbidity lower than expected. One of the possible explanations is the different anti-atherogenic capacity of anti-hypertensive drugs. Reduction of high blood pressure has, by itself, an anti-atherogenic effect, but, for some anti-hypertensive drugs, there is experimental and clinical evidence of anti-atherogenic properties. For calcium antagonists experimental data have been published reporting reduction of aortic lipidic deposition and decrease of arterial proliferation. The INTACT trial has shown that the development of new atherosclerotic lesions was delayed by nifedipine. For beta-blockers, in spite of the negative effect on atherogenic fractions, the experimental evidence, so far collected, suggests a possible anti-atherogenic effect. ACE inhibitors have been experimentally studied and its anti-atherogenic effect reported on studies with the WHHR rabbit and cynomolgus monkey. The different possible mechanisms for these anti-atherogenic properties are analysed. Ketanserine is a serotonin antagonist witch anti-atherogenic capacity is under investigation on the PACK trial. The results that were published so far seem to confirm that capacity.
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PMID:Antihypertensive treatment and regression of atherosclerosis. 138

The relationship between experimental magnesium deficiency and blood pressure is complex and still the subject of much debate. The effect of Mg deficiency and blood pressure in Wistar rats receiving a Mg deficient diet (0.080 g/kg) for 40 weeks was examined. Deficient rats, when compared to controls, showed an initial transitory phase of hypotension, followed by normalization of blood pressure and then hypertension beginning after 15 weeks on the deficient diet. During the whole experimental period, heart rate was significantly increased in deficient rats as compared to controls. The fact that hypotension resulting from Mg deficiency of short duration can be inhibited by antihistamines and by indomethacin suggests that various mediators seen during the inflammatory period of Mg deficiency could be involved. Mg deficiency of long duration was accompanied by hypertension. When Mg-deficient rats received the control diet for a period of 3 weeks, Mg supplementation only partially corrected the hypertension. The hypertension was not a consequence of stimulation of the renin-angiotensin system since the plasma renin activity was not modified and ACE activity was reduced. These deficient rats showed a significantly lower vasopressor response to noradrenaline than control rats. Several factors such as increase in collagen, changes in elastin and arterial elasticity, total lipid content, and calcifications may account for the hyporesponsiveness to contractile agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Magnesium and blood pressure. I. Animal studies. 139 7

Increases of triglycerides and total cholesterol have been reported during treatment with antihypertensive drugs, most notably with beta blockers and diuretics. ACE inhibitors, on the other hand, are not known for having a negative effect on lipid profile. To evaluate the effects of a fixed combination of captopril and hydrochlorothiazide on lipid metabolism, blood pressure, and quality of life, we performed an open prospective study. A total of 2,154 patients with or without hypercholesterolemia, but not receiving lipid lowering drugs, were enrolled. Of the 1891 evaluable patients at baseline, 34.1% had a moderate risk with total cholesterol between 5.2 and 6.5 mmol/l (mean 5.8 mmol/l) and 41.3% had a high coronary heart disease (CHD) risk with total cholesterol higher than 6.5 mmol/l (mean 7.3 mmol/l). After six months of treatment, the median cholesterol level in the moderate risk group decreased from 5.8 to 5.4 mmol/l (p less than 0.0003) and in the high risk group from 7.3 to 6.3 mmol/l (p less than 0.0001). Triglycerides also decreased, whereas high density lipoprotein (HDL) increased in both risk groups. Systolic and diastolic blood pressure fell as expected and quality of life improved. The fixed combination was well tolerated. We observed a significant improvement of lipid profile in patients with mild to moderate hypertension while undergoing treatment with the fixed combination of captopril and hydrochlorothiazide. We suggest that captopril may balance the negative effects of hydrochlorothiazide on lipid metabolism in patients with hypertension and concomitant hyperlipidemia.
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PMID:A "lipo-protective" effect of a fixed combination of captopril and hydrochlorothiazide in antihypertensive therapy. 139 99

In patients with diabetes mellitus, metabolic control, hypertension and kidney function are important prognostic factors. In this respect ACE inhibitors exhibit, according to previous publications, a potentially beneficial effect on diabetic patients. To further clarify this effect of ACE inhibitors, a meta-analysis of 21 studies of type I and II diabetics under therapy with ACE inhibitors was performed. Altogether 325 cases were analyzed. The duration of diabetes varied between 2.5 and 22 years. Therapy with ACE inhibitors under long-term treatment (up to 12 months) reduced diastolic blood pressure (-25%) and, both for type I and II diabetics, fasting blood sugar (-14%) and HbA1 (-9%). Microalbuminuria/proteinuria was reduced by 33% under short-term treatment with ACE inhibitors (up to 3 months) and by 66% under long-term treatment. Analysis of the subgroups with microalbuminuria (30-300 mg/day, n = 48) or clinical proteinuria (greater than 300-1500 mg/day, n = 9) showed similar results. The outcome of this meta-analysis shows that the treatment of diabetic patients with ACE inhibitors not only effectively reduces high blood pressure but also reduces microalbuminuria/proteinuria and, in addition, exhibits an anti-hyperglycemic effect by improving blood sugar levels.
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PMID:[Improved glucose regulation and microalbuminuria/proteinuria in diabetic patients treated with ACE inhibitors. A meta-analysis of published studies of 1985-1990]. 141 95


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