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Biomedical subjects

K O Stumpe

Publications and source records attributed to K O Stumpe.

At least 19 recordsLinked to original sources
PubMed1992

Angiotensin-converting enzyme inhibition in mild hypertension with concomitant diseases and therapies: an efficacy, safety, and compatibility study of novel design, the Perindopril Therapeutic Safety Study.

Despite a marked reduction in cardiovascular morbidity and mortality, treated hypertensive patients remain at increased risk of coronary artery disease and its complications compared with untreated normotensive subjects. Mild hypertension is often associated with other, usually chronic, diseases. The failure of first-line antihypertensive therapy to deal adequately with concomitant disease and associated therapy might account for the poor improvement in the cardiovascular prognosis. This possibility has been addressed in an ongoing trial of novel design, the Perindopril Therapeutic Safety Study, a multicenter, double-blind, randomized and placebo-controlled trial to determine the safety, efficacy, and interaction of angiotensin-converting enzyme (ACE) inhibition with eight of the most common concomitant diseases and their therapies. A total of 480 male and female patients (60 per disease group) aged 30-70 years, with a diastolic pressure of 90-104 mm Hg, were included after a 3-week placebo run-in if they satisfied standard criteria for any of the following: hyperlipidemia, type II diabetes, ischemic heart disease, cardiac arrhythmia, peripheral arterial disease, nephropathy with proteinuria, chronic obstructive lung disease, or rheumatoid arthritis. Of these, 460 patients have completed the 6-week double-blind phase (comprising two assessments, at 3 and 6 weeks), and are currently undergoing assessments every 3 months over a 1-year follow-up period. The end points include the incidence of progression or improvement in concomitant disease, the incidence of positive or negative interaction between ACE inhibition and concomitant therapy, change in blood pressure, adverse biochemical and hemodynamic reactions, self-reported side effects, and quality of life indices. Interim results for the 6-week double blind phase will shortly be available. However, the desirability and feasibility of conducting a study according to this novel design have already been proved.

Adult↗
PubMed1992

Effects of a high-cholesterol diet on arterial wall thickness and vascular reactivity in young rabbits.

Cholesterol enrichment of arteries may induce biochemical and structural abnormalities in vascular smooth muscle resulting in increased arterial contractile sensitivity. We studied the effects of a high-cholesterol diet on arterial structural properties and vascular reactivity in young rabbits. In vivo measurements of aortic intimal-plus-medial thickness using high resolution ultrasound imaging were obtained before and after 3 weeks of a high-cholesterol diet in 12 rabbits (group 2) and compared to data from 12 animals a cholesterol-free diet fed (group 1). Six rabbits (group 3) were studied before and after a 3-week, high-cholesterol diet and after a subsequent 13-week, cholesterol-free recovery diet. Blood pressure responsiveness to noradrenaline was evaluated before and at the end of each diet period. In groups 2 and 3, high dietary cholesterol caused an increase in intimal-plus-medial thickness from 0.31 mm and 0.33 mm to 0.88 mm and 0.89 mm, respectively (p less than 0.001). Plasma cholesterol concentration rose from 0.9 +/- 0.26 mmol/l to 36.7 +/- 8.56 mmol/l. There was no change in group 1. In group 3, intimal-plus-medial thickness remained increased (1.01 mm) following the cholesterol-free recovery diet despite normal plasma cholesterol. Blood pressure responsiveness to noradrenaline was markedly increased after the high-cholesterol diet (p less than 0.001) in groups 2 and 3 and after the cholesterol-free recovery diet in group 3 (p less than 0.001), and was directly related to intimal-plus-medial thickness (r = 0.84; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Antihypertensive therapy: new strategies beyond blood pressure control.

Mild-to-moderate essential hypertension is the most common medical problem seen by physicians in Western populations, and pharmacologic antihypertensive therapy is now usually undertaken. Clinical trials have shown that lowering of elevated blood pressure using diuretics and beta-blockers reduces cardiovascular morbidity and mortality. Despite these benefits, the trials have provided no convincing evidence that the incidence of coronary artery disease or its complications is reduced: Treated hypertensive patients remain at increased cardiovascular risk compared with untreated normotensive subjects. Possible explanations for this disappointing outcome are that the drugs used may themselves have negative effects on serum lipids, glucose, and insulin resistance, thereby outweighing their antihypertensive benefits. An equally important role in this respect may be played by the diseases and therapies most commonly found in association with mild-to-moderate hypertension: hyperlipidemia, type II diabetes, coronary artery disease, left ventricular hypertrophy, cardiac arrhythmias, peripheral arterial disease, and nephropathy. Such conditions may be potent determinants of what constitutes the optimal first-line choice of antihypertensive therapy. Furthermore, the negative effects that antihypertensive drugs can have on quality-of-life factors may result in noncompliance and ineffective long-term treatment. Therefore, in a new therapeutic approach to the treatment of high blood pressure, it would be logical to base antihypertensive therapy on strategies that not only lower the blood pressure but that have beneficial impacts on hemodynamics, vascular and cardiac structure, metabolism, and quality-of-life issues.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1992

Cough induced by ACE-inhibitors. A kinin related phenomenon?

Cough induced by ACE-inhibitors may be related to bronchial hyperreactivity and/or to an accumulation of kinins. In a placebo-controlled, double-blind randomized study in asthmatic and hypertensive patients lung function and bronchial reactivity to histamine and bradykinin remained unaltered although in hypertensive patients with cough, reactivity to histamine tended to be more pronounced and bronchial hyperreactivity to be more frequent than in those without cough. The findings do not support a major role of kinins in ACE inhibitor-induced cough.

Adult↗
PubMed1992

Airway responsiveness and cough induced by angiotensin converting enzyme inhibition.

Dry cough is one of the most common side-effects of angiotensin converting enzyme inhibitors. The mechanism of cough induced by ACE inhibitors is not completely understood and may be related to bronchial hyperreactivity and/or an accumulation of kinins. In a placebo-controlled, double-blind randomised study, the effect of captopril on lung function and bronchial reactivity to histamine and bradykinin was investigated in eight asthmatic and 12 hypertensive patients (six with and six without cough during previous ACE inhibition). Lung function did not change in any patient after a single (25 mg) or short-term (2 x 25 mg for two weeks) administration of captopril. Bronchial reactivity to histamine and bradykinin remained unaltered in all groups. In hypertensive patients with cough, reactivity to histamine tended to be more pronounced and bronchial hyperreactivity to be more frequent than in those without cough. In conclusion, the present results do not support a major role for kinins in cough induced by ACE inhibition. On the other hand, bronchial hyperreactivity may be important in some patients. Additionally, these results demonstrate that treatment with ACE inhibitors is safe in most patients with bronchial asthma.

Adult↗
PubMed1991

Chronic kappa-opioid receptor antagonism delays the rise in blood pressure in spontaneously hypertensive rats.

A 4-week subcutaneous treatment with the kappa-opioid receptor antagonists, MR 2266 or MR 1452, delayed the age-dependent increase in systolic blood pressure in young spontaneously hypertensive rats (SHR), but not in normotensive rats. The content of beta-endorphin, [Leu5]enkephalin, and catecholamines in various brain tissues was not affected by MR 2266. Specificity of the kappa-opioid receptor antagonism was tested in SHR by injection of the kappa-opioid agonist, MR 2033, and the mu agonist, morphiceptin, after 28 days of MR 1452 or saline and 2 days after the end of treatment. The increase in mean arterial blood pressure (MAP) after MR 2033 did not differ between the two groups at the 28th day of treatment but was higher 2 days later in the previous MR 1452 group, possibly indicating up-regulation of kappa-opioid receptors. Morphiceptin did not alter MAP during or after MR 1452. It is concluded that kappa-opioid receptors may have a tonic influence on the age-dependent increase of blood pressure in SHR but not in normotensive rats.

Adrenal Glands↗
PubMed1991

[Effectiveness of pravastatin and bezafibrate in primary hypercholesterolemia].

The efficacy and safety of pravastatin and bezafibrate (in retard form) were compared in a randomised double-blind trial comprising 96 patients (48 men, 48 women; mean age 52.5 [20-68] years) with primary hypercholesterolaemia types IIa and IIb. After four weeks' treatment 6 out of 38 patients (400 mg/d bezafibrate) and 27 out of 58 patients (20 mg/d pravastatin) reached a LDL cholesterol level of 190 mg/dl or less. In the other 31 patients of the pravastatin group the dose was raised to 40 mg/d. During the twelve-week course of pravastatin total cholesterol concentration fell from a mean of 364 +/- 75 mg/dl (initial value) to 281 +/- 61 mg/dl (P less than 0.01), while LDL-cholesterol fell from 288 +/- 81 mg/dl to 206 +/- 64 mg/dl (P less than 0.01) and triglyceride concentration from 168 +/- 83 mg/dl to 148 +/- 80 mg/dl (P less than 0.05). During the twelve-week course of treatment with 400 mg bezafibrate total cholesterol concentration fell from a mean of 363 +/- 91 mg/dl to 325 +/- 73 mg/dl (P less than 0.01), LDL-cholesterol level fell from 284 +/- 88 mg/dl to 242 +/- 70 mg/dl (P less than 0.01) and the triglyceride concentration from 173 +/- 91 mg/dl to 121 +/- 83 mg/dl (P less than 0.01). HDL cholesterol concentration rose by 9% in the bezafibrate group and by 8.4% in the pravastatin group (P less than 0.05). Except in the case of HDL-cholesterol, the falls were significantly different in the two treatment groups: pravastatin was superior to bezafibrate in terms of the reductions in both total and LDL-cholesterol (P less than 0.01 for each). However, bezafibrate produced a greater fall in serum triglycerides (P less than 0.05). No serious side effects were associated with either drug.

Adult↗
PubMed1991

A double-blind comparison of perindopril and hydrochlorothiazide-amiloride in mild to moderate essential hypertension.

The aim of this 3-month double-blind multicenter trial was to compare the antihypertensive efficacy and tolerability of the ACE inhibitor perindopril with those of a diuretic combination. After 1 month of receiving placebo, 165 patients with essential hypertension were randomised to perindopril 4 mg (n = 82) or to 50 mg hydrochlorothiazide + 5 mg amiloride (n = 83). The patients were treated for 3 months with monthly assessments, "uncontrolled" patients (DBP greater than 90 mm Hg) had their dosage doubled and then, if necessary, atenolol 50 mg was added. At the end of the 3-month study, mean decreases in supine and standing systolic and diastolic blood pressures were similar in both groups. In the perindopril group, BP control was obtained in 56% of the patients with the 4 mg dosage and required an increase to 8 mg alone in 16% and with atenolol in 5%. The corresponding percentages in the diuretic group were 48, 23 and 13%. The overall percentage of "controlled" patients was similar in the 2 groups, respectively 78 and 84%. The nature and incidence of complaints were comparable in the 2 groups. Adverse laboratory changes were more frequent in the diuretic group: decrease in blood sodium (140.5 vs 139.1 mmol/l; P less than 0.01), potassium (4.2 vs 3.9 mmol/l; P less than 0.01) with 10 patients having significant hypokalemia, increase in blood urea, triglycerides and uric acid. By contrast, a transient increase in blood potassium with a decrease in triglycerides was observed in the perindopril group.

Adolescent↗
PubMed1991

Influence of chronic opioid delta receptor antagonism on blood pressure development and tissue contents of catecholamines and endogenous opioids in spontaneously hypertensive rats.

Opioid delta receptors seem to be involved in blood pressure regulation of spontaneously hypertensive rats (SHR), possibly by an interaction with the sympathetic nervous system. In the present study the effect of four weeks' chronic delta receptor antagonism with ICI 154 129 on development of blood pressure was evaluated in young SHR. Contents of adrenaline and noradrenaline and the opioid peptides beta-endorphin and leucine-enkephalin were measured in brain stem, mid brain, hypothalamus, and adrenal glands. After four weeks' treatment, systolic blood pressure was lower when compared with control SHR. During chronic delta antagonism, concentrations of adrenaline were higher in hypothalamus, mid brain and adrenal glands, contents of noradrenaline were higher in hypothalamus and adrenal glands than in control rats, contents of opioid peptides were not altered with the exception of an increase of beta-endorphin concentration in the hypothalamus. The changes in concentrations of catecholamines following chronic delta antagonism may reflect an alteration of sympathetic activity and could contribute to the retardation of blood pressure development.

Animals↗
PubMed1991

Membrane transport, sodium balance, and blood pressure regulation.

Essential hypertension is characterized by polygenic inheritance and quantitative and/or qualitative abnormalities of membrane transport systems may function as intermediate phaenotypes. The present review attempts to evaluate the importance of sodium transport systems such as the sodium pump, cotransport and countertransport as aetiological or pathogenetic factors involved in primary hypertension. Furthermore, the relative importance of NaCl balance as an exogenous factor modifying these transport systems is reviewed. Controversial results exist with respect to the activity of the sodium pump and cotransport both as a function of blood pressure and NaCl balance. In contrast, accumulating evidence suggests that the activity of the counter-transport system is increased in essential hypertension and that this may be observed even before the elevation of blood pressure can be documented. In own studies performed in normotensive volunteers on a low (20 mmol/day) and high (320 mmol/day) NaCl intake, lymphocyte antiport activity was significantly higher during chronic NaCl loading. Therefore, alterations of the Na+/H+ antiport system may represent an intermediate phaenotype of gene(s) involved in the genesis of primary hypertension. Preliminary evidence suggests that NaCl balance may be an exogenous modulator of this system.

Animals↗
PubMed1991

Short-term dietary sodium restriction increases serum lipids and insulin in salt-sensitive and salt-resistant normotensive adults.

Evidence suggests that dietary salt reduction similar to diuretic therapy may adversely affect lipid and glucose metabolism. We studied 147 non-obese normotensive subjects (60 females and 87 males) aged 19-78 years who entered a single-blind crossover trial and were randomly assigned to a low salt diet of 20 mmol or a high salt diet of 300 mmol sodium per day, for 7 days each. Sodium restriction lowered mean arterial blood pressure (MAP) by a mean of 7.5 mmHg in 17% (salt-sensitive), had no hemodynamic effect in 67% (salt-resistant) and raised MAP by a mean of 6 mmHg in 16% of the subjects (reverse reactors). With dietary salt restriction serum total- and LDL-cholesterol as well as serum insulin and uric acid concentrations increased significantly in all three groups. The largest increases in total (10%) and LDL- (12%) cholesterol occurred in the reverse reactors. Salt-sensitives had significant higher lipoprotein(a) values than the other two groups. Salt-restriction had no significant effect on this parameter. Plasma renin activity, as well as plasma aldosterone and noradrenaline concentrations rose in all three groups during the low salt diet, the largest increases being observed in the reverse reactors. Short-term sodium restriction in normotensive adults has unfavourable effects on lipid and glucose metabolism, especially in subjects who do not derive hemodynamic benefit. Further studies are necessary to examine the effects of more moderate salt reduction for longer periods on the risk factor profile for cardiovascular disease before a low salt diet can be regarded as a safe public health measure for the general population.

Adult↗
PubMed1991

The influence of oral potassium citrate/bicarbonate on blood pressure in essential hypertension during unrestricted salt intake.

In several trials, a blood pressure lowering effect of potassium chloride could be demonstrated. However, it is not known if other potassium salts are also effective. In a randomized cross-over trial, 12 patients with essential hypertension were treated for 8 weeks with placebo and 120 mmol potassium per day. Potassium was given together with 50% citrate and 50% bicarbonate as anions. Urinary potassium excretion rose from 61.8 +/- 8.1 to 166.7 +/- 21.2 mmol/24 hours during potassium supplementation. However, blood pressure and heart rate remained unchanged when compared to placebo. Non-chloride potassium salts may not be effective in lowering blood pressure in essential hypertension. Since potassium rich foods like fruits and vegetables contain potassium mostly as non-chloride salts, it appears to be premature to recommend a high dietary potassium intake as a mean to treat elevated blood pressure.

Adult↗
PubMed1990

[Therapy of moderate hypertension with the calcium antagonist nitrendipine in combination with beta receptor blocker or diuretic].

The efficacy of the calcium channel blocker nitrendipine alone and in combination with the beta blocking agent acebutolol or hydrochlorothiazide was tested in 34 patients with moderate essential hypertension. After a wash out period of three to four weeks, all patients received placebo for two weeks, thereafter 20 mg of nitrendipine per day for four weeks. When diastolic blood pressure remained above 95 mmHg with nitrendipine, acebutolol (200 mg/d) or the thiazide (25 mg/d) was added in a randomised double-blind fashion. With nitrendipine alone, blood pressure could be normalized in nine patients with a drop in pressure from 168/108 to 152/89 mmHg. The other patients showed a fall in blood pressure from 164/110 to 152/102 mmHg. In these patients, the addition of acebutolol or thiazide was followed by a further fall in blood pressure which was similar with both drugs. With acebutolol blood pressure decreased from 154/102 to 146/94 mmHg and with the thiazide from 152/102 to 147/95 mmHg, respectively. Minor and mostly transient side effects were predominantly seen during therapy with nitrendipine alone. The fall in diastolic but not systolic blood pressure with nitrendipine was correlated with age. The blood pressure lowering effect of nitrendipine was independent of plasma renin activity and intracellular electrolyte concentrations. In the therapy of moderate hypertension, nitrendipine given in combination with a betablocker or a thiazide diuretic is effective and well tolerated.

Acebutolol↗