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

We performed renal function studies in dogs with chronic renovascular hypertension produced by complete occlusion of a renal artery. In addition, we evaluated in anesthetized dogs the acute effects of a novel angiotensin converting enzyme inhibitor, CGS 16,617, on renal function and plasma neurohormones (epinephrine, norepinephrine and vasopressin) 4 weeks after initiation of 2 kidney, 1 clip hypertension. CGS 16,617 effectively decreased blood pressure in renal hypertensive animals. This response was associated with suppression of angiotensin II indicating effective converting enzyme inhibition. In the non-clipped kidney, acute administration of CGS 16,617 increased effective renal plasma flow but not glomerular filtration rate and urinary sodium excretion. In the clipped kidney, CGS 16,617 caused no change in any parameter of renal function. Plasma norepinephrine, epinephrine and vasopressin were unaffected by administration of CGS 16,617. These studies showed that chronic occlusion of a renal artery does not result in renal infarction because of a compensatory increase in the amount of blood provided through capsular collateral vessels. The collateral circulation which has developed in the clipped kidney explains the lack of a converting enzyme inhibitor effect.
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PMID:Patterns of renal function in hypertension due to unilateral renal artery occlusion. 135 85

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

We have evaluated the genes for angiotensin converting enzyme (ACE) and guanylyl cyclase A/atrial natriuretic peptide receptor (GCA) for genetic effects on blood pressure response to high salt diet. In F2 rats derived from Milan normotensive and Dahl salt-hypertension sensitive (S) rats, both ACE and GCA cosegregated with blood pressure, and rats that were homozygous for the S allele at both the ACE and GCA loci had inordinately high blood pressure. In F2 derived from Wistar Kyoto (WKY) and S rats, GCA revealed positive cosegregation with blood pressure, but ACE did not. We conclude that certain alleles at the GCA and ACE loci (or at loci closely linked to them) have a significant genetic impact on blood pressure response to high salt in specific rat strains.
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PMID:Cosegregation of blood pressure with angiotensin converting enzyme and atrial natriuretic peptide receptor genes using Dahl salt-sensitive rats. 136 13

Enalapril, an angiotensin converting enzyme (ACE) inhibitor usually administered orally once daily, decreases blood pressure by lowering peripheral vascular resistance without increasing heart rate or output. It is effective in lowering blood pressure in all grades of essential and renovascular hypertension. Patients not responding adequately to enalapril monotherapy usually respond with the addition of a thiazide diuretic (or a calcium antagonist or beta-blocker), and rarely require a third antihypertensive agent. Enalapril is at least as effective as other established and newer ACE inhibitors, and members of other antihypertensive drug classes including diuretics, beta-blockers, calcium antagonists and alpha-blockers, but therapy with enalapril may be less frequently limited by serious adverse effects or treatment contraindications than with other drug classes. The most frequent adverse effect limiting all ACE inhibitor therapy in clinical practice is cough. This favourable profile of efficacy and tolerability, and the substantial weight of clinical experience, explain the increasing acceptance of enalapril as a major antihypertensive treatment and supports its use as logical first-line therapeutic option.
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PMID:Enalapril. A reappraisal of its pharmacology and therapeutic use in hypertension. 137 19

Hypertension is often seen in Type 1 and Type 2 diabetic patients, particularly in those with nephropathy, and the progression of diabetic nephropathy is closely related to blood pressure elevation. Thus, the effects of antihypertensive drugs on kidney function and insulin sensitivity in diabetic patients are of great clinical importance. Successful antihypertensive treatment has been shown to slow the progression of diabetic nephropathy. Several results from short term studies have suggested that angiotensin converting enzyme (ACE) inhibitors may be advantageous over other conventional antihypertensive agents in reducing albuminuria in both hypertensive and normotensive diabetics with microalbuminuria or persistent proteinuria. However, the decline in glomerular filtration rate during ACE inhibitor treatment is comparable to that during effective treatment with conventional antihypertensive drugs in hypertensive Type 1 diabetic patients with overt nephropathy. Whether ACE inhibitors possess a specific effect in preventing the development of diabetic nephropathy remains to be seen in properly designed long term studies. Although calcium antagonists may preserve kidney function or possess a renoprotective effect in hypertensive Type 2 diabetics with nephropathy, firm evidence supporting this contention seems to be lacking and also requires long term evaluation. Increasing attention is being directed toward the effect of antihypertensive drugs on insulin sensitivity in diabetic patients: ACE inhibitors and alpha 1-adrenoceptor blocking agents have been shown to improve this sensitivity. Despite the widespread involvement of calcium in hormone secretion and action, calcium antagonists appear to have little effects on the glucoregulatory and calcium-regulatory hormones within the drug dosages used in clinical practice. Several clinical variables, such as the presence or absence of hypertension, overt nephropathy and microalbuminuria, or a combination of variables should be accounted for when evaluating critically the cumulative data on the effects of antihypertensive drugs on kidney function and albuminuria in the variety of diabetic patient groups. Understanding the pharmacokinetic and pharmacodynamic characteristics of antihypertensive drugs will be of clinical importance in diabetic patients with advanced nephropathy (glomerular filtration rate of less than 30 ml/min) and/or other complications, such as impaired gastric motility or gastroparesis, and will thereby lead to a more rational management of hypertension in those patients.
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PMID:Recent advances in pharmacological management of hypertension in diabetic patients with nephropathy. Effects of antihypertensive drugs on kidney function and insulin sensitivity. 137 14

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

Idrapril is the prototype of a new chemical class of angiotensin converting enzyme (ACE) inhibitors, the hydroxamic non-amino acid derivatives. Idrapril strongly inhibited rat and human plasma ACE and rabbit lung ACE (IC50: 7-12 nM) as well as the pressor response induced by angiotensin I in anesthetized rats (ED50: 63 nmol/kg i.v.). Idrapril (0.04-23 mumol/kg i.v.) lowered the blood pressure dose dependently, up to 20-35%, in different models of hypertension (sodium-depleted spontaneously hypertensive rat, two-kidney-one-clip renal hypertensive rat, and aortic-coarctated rat), its profile being similar to that of captopril in terms of potency and efficacy. Idrapril and captopril reduced the blood pressure and potentiated substance P-induced bronchoconstriction in the guinea pig to the same extent, suggesting a similar degree of ACE inhibition in the circulation. However, idrapril potentiated capsaicin-induced bronchoconstriction (a model that has been related to the liability of ACE inhibitors to produce cough in patients) less effectively than captopril. We conclude that effective ACE inhibition in vitro and in vivo can be obtained with this novel class of compounds.
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PMID:Pharmacology of idrapril: a new class of angiotensin converting enzyme inhibitors. 138 23


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