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

Inhibitors of the angiotensin-converting enzyme (ACE = kininase II) by definition have a dual action: prevention of angiotensin II generation and inhibition of kinin degradation. Although the first mechanism is generally accepted, it may not by itself be sufficient to explain the acute blood pressure-lowering action of these compounds. Studies in experimental and clinical hypertension, including the use of selective angiotensin II and bradykinin receptor antagonists, suggest additional vasodilator, non-renin-dependent mechanisms in their action on blood flow and blood pressure. Inhibition of kinin degradation by ACE inhibitors will amplify kinin-mediated reactions on local vessel tone, in particular, if kinin generation is stimulated or this situation is experimentally mimicked by addition of exogenous bradykinin. The acute blood pressure-lowering action of ACE inhibitors is inhibited by indomethacin-type cyclooxygenase inhibitors, suggesting a contribution of bradykinin-induced release of vasodilator prostaglandins to their action. Bradykinin stimulates the phospholipase-dependent release of arachidonic acid from membrane phospholipids, allowing for subsequent generation of its metabolites, the eicosanoids. This stimulation is receptor-mediated and involves one or more types of B2 receptors, coupled via G-proteins to intracellular messenger systems that control cytosolic calcium levels. Bradykinin-induced changes in vessel tone are transient, caused by a rapidly developing tachyphylaxis at the receptor level. The potent vasodilator action of systemic bradykinin administration is not consistently reflected in studies performed on isolated blood vessels. This is probably due to the indirect nature of kinin-mediated vasomotor responses, i.e., the release of vasoactive mediators, most notably the eicosanoids and endothelium-derived relaxing factor (EDRF).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Converting enzyme inhibitors and the interaction between kinins and eicosanoids. 169 63

In hypertension, increased systolic blood pressure (BP) and the resulting increase in systolic wall stress are major determinants of the degree of left ventricular hypertrophy (LVH). Antihypertensive drugs all decrease BP, but different classes of these drugs may activate other trophic mechanisms and therefore may have different effects on LVH. Angiotensin-converting enzyme (ACE) inhibitors decrease the major cardiac growth-promoting factors such as systolic wall stress, diastolic wall stress, and cardiac sympathetic and renin activity, and consistently cause regression of LVH. On the other end of the drug spectrum, arterial vasodilators may decrease systolic wall stress, but increase diastolic wall stress and cardiac sympathetic and renin activity, resulting in either the absence of regression or even progression of LVH. Other classes of antihypertensive drugs nonuniformly change neural, humoral, or mechanical stimuli, so that the net effect ranges from full regression, partial regression, to none. Age and reactivity of sympathetic and/or renin activity may play a major role in determining the response of cardiac mass to BP lowering.
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PMID:Antihypertensive drugs and cardiac trophic mechanisms. 171 86

Bradykinin is a potent vasodilator peptide; however, its half-life in vivo is very short because of various plasma and tissue peptidases that hydrolyze bradykinin to inactive fragments. We studied the role of kininase II (angiotensin converting enzyme) and neutral endopeptidase 24.11 (enkephalinase) in the catabolism of bradykinin in vascular tissue by determining the effect of inhibitors of kininase II (captopril) and of endopeptidase 24.11 (phosphoramidon) on the action of bradykinin on rat isolated mesenteric arteries. Because bradykinin may induce prostaglandin formation and release, we also studied the effect of a cyclooxygenase inhibitor, indomethacin, on the action of bradykinin. The mesenteric bed was isolated from rats (250-300 g) with rats under either anesthesia and was perfused with Krebs' solution (4 ml/min) containing phenylephrine (0.5-1.0 microgram/ml) to produce a mean perfusion pressure of 120-130 mm Hg. Bradykinin (2.5-40.0 ng), injected as a bolus, produced a dose-dependent decrease in perfusion pressure. In the presence of indomethacin (1.0 microgram/ml), the amplitude of the vasodilator responses to bradykinin was not significantly affected, although the duration of the responses was increased approximately two to four times. In the presence of captopril (1.0 microgram/ml), bradykinin elicited either a vasodilator or a biphasic effect. The vasodilator effect was greatly potentiated by captopril, whereas the duration of the response was unchanged when compared with control experiments. When present, the pressor responses were also dose related. In the presence of indomethacin plus captopril, bradykinin produced only a fall in perfusion pressure that lasted five to six times longer than without any treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Effect of bradykinin on isolated mesenteric arteries of the rat. 173 87

Late diabetic effects are the sequelae of for a long time super elevated blood sugar levels. The diabetic nephropathy is the cause of the secondary arterial hypertension. The investigation seeks for the connections between the diabetes mellitus and the essential, that is primary hypertension. The two diseases frequently appear and clearly increase in the second half of life. Moreover, they are above average frequently associated with each other. Among brothers and sisters of diabetic hypertensives in comparison to normal cohorts clearly increased high blood pressure prevalences were found. The insulin resistance which could be proved in a great number of hypertensive and which has been known since more than two decades might be the connecting link between hypertension and diabetes mellitus. Like the obesity the essential hypertension can be associated with all degrees of an insulin hyposensitiveness. The sodium-retaining effect of the insulin might explain the increased sodium content of the body in hypertensives. The differential diagnostics of the essential hypertension should therefore seek for conditions of an insulin resistance. The type II diabetic lacks a release of bradykinin during muscle work. Thus the glucose uptake into the cell is unfavourable influenced and demands an increased insulin excretion. This genetically (?) fixed defect is found also in essential hypertensives. It could be the connecting link between the two diseases. ACE-inhibitors have via a kininase II inhibition an effect also on the bradykinin decomposition and can favourable influence the glucose uptake into the muscle. An improved insulin effect among the ACE-inhibitors was described. Therefore, they should be preferred in the treatment of hypertensive diabetics.
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PMID:[Diabetes mellitus and arterial hypertension. In search of the connecting link]. 177 26

The close relationship between diabetes and hypertension has been recognized for decades. New information indicates that resistance to insulin action on glucose uptake in peripheral tissues is a common underlying mechanism in hypertension and diabetes. In prospective trials, the effects of antihypertensive agents on insulin sensitivity and lipoprotein metabolism have been evaluated. Both beta-blockers and thiazide diuretics worsen insulin resistance and deteriorate lipoprotein metabolism. Angiotensin-converting enzyme (ACE) inhibitors, Ca2(+)-channel blockers, and alpha-blockers are neutral or improve these factors. These data may explain the unexpectedly high incidence of the development of diabetes among treated hypertensives and the poor effect on risk for coronary heart disease in intervention trials.
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PMID:Effect of antihypertensive drugs on insulin, glucose, and lipid metabolism. 182 17

Research in nephrologic nuclear medicine is presently concentrated in two well-defined areas: interventional procedures and the use of mercaptoacetyltriglycine. The ongoing evaluation of mercaptoacetyltriglycine continues to be a source of interesting research activity, with the distribution volume and the extent of hepatic excretion remaining points of discussion. This tracer permits quantitative determination of renal function. As an imaging agent, mercaptoacetyltriglycine compares favorably with hippurate and with diethylenetriamine penta-acetic acid, particularly in evaluating renal insufficiency. Renal function studies obtained during pharmacologic or physiologic intervention dominate research in hypertension and obstructive uropathy. Angiotensin-converting enzyme inhibition improved the renographic detection of renovascular lesions. Interventional renography with angiotensin-converting enzyme inhibition or ergometric exercise were both capable of generating useful prognostic data on the posttherapy blood pressure response in patients with renovascular hypertension. Interventional diuretic renography with furosemide permits surgical intervention to be reserved for organs at immediate risk because the degree of obstruction and the extent of renal function compromise are easily recognized.
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PMID:Renal studies in nuclear medicine. 183 42

Angiotensin-converting enzyme (ACE) and enkephalinase, two cell surface metallopeptidases, are responsible for angiotensin II formation and atrial natriuretic factor (ANF) degradation, respectively, and thereby play a critical role in the metabolism of hormonal peptides exerting essentially opposite actions in cardiovascular regulations. To affect simultaneously both hormonal systems by a single molecular structure, we have designed glycoprilat and alatrioprilat [(S)-N-[3-(3,4-methylene-dioxyphenyl)-2-(mercaptomethyl)-1-oxoprop yl] glycine and -alanine, respectively]. In vitro the two compounds inhibit both ACE and enkephalinase activities with similar, nanomolar potencies, and in vivo, glycopril and alatriopril, the corresponding diester prodrugs, occupy the two enzyme molecules in lung at similar low dosages (0.2-0.5 mg/kg of body weight, per os). The high potency of these compounds is attributable to interaction of the methylenedioxy group with the S1 subsite of ACE and of the aromatic ring with the S1' subsite of enkephalinase. In rodents, low doses of these mixed inhibitors exert typical actions of ACE inhibitors--i.e., prevention of angiotensin I-induced hypertension--as well as of enkephalinase inhibitors--i.e., protection from 125I-ANF degradation or enhancement of diuresis and natriuresis following acute extracellular volume expansion. In view of the known counterbalanced physiological actions of the two hormonal peptides, whose metabolism is controlled by ACE and enkephalinase, mixed inhibitors of the two peptidases show promise for the treatment of various cardiovascular and salt-retention disorders.
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PMID:Mixed inhibitors of angiotensin-converting enzyme (EC 3.4.15.1) and enkephalinase (EC 3.4.24.11): rational design, properties, and potential cardiovascular applications of glycopril and alatriopril. 185 98

Angiotensin-converting enzyme (ACE) inhibitor therapy has been reported to improve patient survival and promote recovery of renal function in the renal crisis of systemic sclerosis. In addition, an ACE inhibitor and a calcium channel blocker have been reported to control hypertension and reverse dialysis-dependent renal failure in a patient with undifferentiated connective tissue disease. We treated a patient with undifferentiated connective tissue disease who developed hypertension, pulmonary compromise, and renal failure requiring prolonged dialysis therapy. Due to allergy, the patient's hypertension could not be treated with ACE inhibitors initially, yet pulmonary function improved and renal function partially recovered with tenormin and minipress. When blood pressure became refractory to tenormin and minipress after 14 months of peritoneal dialysis, the patient was treated with lisinopril alone. Pulmonary function has remained stable and the patient has been off renal replacement therapy for 26 months, with a further substantial increase in creatinine clearance following treatment with lisinopril. The delayed and sustained recovery of renal and pulmonary function in the present case suggests undifferentiated connective tissue disease, like systemic sclerosis, may benefit from therapy with ACE inhibitors.
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PMID:Recovery of renal function in undifferentiated connective tissue disease after treatment with angiotensin-converting enzyme inhibitors. 196 60

The presence of left ventricular hypertrophy (LVH) is of poor prognosis in essential arterial hypertension, but it may regress under antihypertensive treatment. Angiotensin-converting enzyme inhibitors, calcium antagonists, centrally acting antihypertensive agents and beta-blockers with low intrinsic sympathomimetic activity constantly reduce the left ventricular mass. This stands in contrast with diuretics and vasodilators which induce stimulation of the sympathetic and/or renin-angiotensin systems and usually have no effect on LVH. Animal experiments have shown that regression of LHV has no adverse effect on the myocardial changes aimed at correcting the LVH-associated abnormalities (collagen content, changes in isomyosins, density of beta-adrenergic receptors, etc.) and that it improves the coronary haemodynamics disturbed by LVH. In clinical practice, reducing the ventricular mass does not modify the left ventricular systolic function, usually improves the diastolic function precociously altered by LVH and seems to reduce the LVH-induced ventricular hyperexcitability. The regression of LVH under antihypertensive treatment should result in a lesser cardiovascular risk in hypertensive patients.
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PMID:[Regression of left ventricular hypertrophy with antihypertensive treatment]. 197 67

Angiotensin-converting enzyme (ACE) inhibitors are now in widespread use for the treatment of essential and renovascular hypertension. Consequently, angioedema, an uncommon complication of ACE inhibitor therapy is being encountered with increasing frequency. Since ACE inhibitor angioedema predominantly involves the face, lips, oral cavity, and occasionally the larynx the otolaryngologist is often consulted to evaluate affected patients. Treatment ranges from simple cessation of the drug to emergent airway intervention. The pertinent pharmacologic properties of ACE inhibitors and the pathophysiology of angioedema are discussed. The authors' experience with the evaluation and treatment of ACE inhibitor induced angioedema is presented.
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PMID:Angiotensin-converting enzyme inhibitor induced angioedema of the head and neck. 208 1


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