Effect of the angiotensin II receptor antagonist MK 954 on the angiotensin II-induced increase in free cytosolic Ca2+ and growth in vascular smooth muscle cells.
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Angiotensin II↗
Biomedical subjects
R Düsing
Publications and source records attributed to R Düsing.
Arterial blood pressure. Correlation with erythrocyte count, hematocrit, and hemoglobin concentration.
The relationship between arterial blood pressure and red blood cell variables was investigated in 1013 unselected persons with a blood pressure range of 90 to 225 mm Hg systolic and 50 to 145 mm Hg diastolic. Statistically significant correlations were demonstrated between mean (as well as systolic and diastolic) arterial blood pressure and red blood cell count (r = 0.27; P less than .0001), hematocrit (r = 0.28; P less than .0001), and hemoglobin concentration (r = 0.29; P less than .0001). Average arterial blood pressure was higher in men than in women (133 +/- 16/83 +/- 10 v 124 +/- 16/79 +/- 9 mm Hg, P less than .0001) and this was associated with higher values for erythrocyte count, hemoglobin concentration, and hematocrit in men as compared to women. The significant correlation of blood pressure and hematocrit, which represents one important determinant of blood viscosity, points to a role for rheological factors in the long-term control of blood pressure. Moreover, it might be speculated that the sex difference in blood pressure as observed in the present study may be due, at least in part, to stimulated erythropoiesis in men as compared to women.
Adult↗
[Hypertension. Individualized treatment as a new therapy concept].
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Antihypertensive Agents↗
Converting enzyme inhibition and vascular prostacyclin synthesis: effect of kinin receptor antagonism.
The effects of angiotensin I-converting enzyme (ACE) inhibitors and bradykinin (BK) on prostacyclin (PGI2) production in isolated arterial tissue were investigated. Rings of rat abdominal aorta were incubated in Krebs-Ringer bicarbonate buffer and PGI2 generation was assessed by the determination of its stable hydrolysis product; 6-keto-PGF1 alpha. The addition of both ACE inhibitors, captopril and lisinopril, and bradykinin resulted in dose-dependent stimulation of PGI2 biosynthesis when the individual substance was added into the incubation buffer at final concentrations between 10(-8) and 10(-5) M. The bradykinin-induced stimulation of PGI2 synthesis was dose dependently inhibited by the BK receptor antagonist, D-Arg[Hyp3, Thi5,8, D-Phe7]BK. The captopril- and lisinopril-induced stimulation of vascular 6-keto-PGF1 alpha production was also significantly decreased when the BK antagonist was added to the incubation medium together with the ACE inhibitors. Our results show that both captopril and lisinopril stimulate PGI2 synthesis in arterial tissue and that this effect may be secondary to changes in the activity of the kinin system.
6-Ketoprostaglandin F1 alpha↗
Effects of n-3 fatty acids on renal function and renal prostaglandin E metabolism.
The present study was performed to investigate the effects of dietary fish oil supplements on renal function and renal prostaglandin (PG) E metabolism. The usual "western" diet of 10 healthy volunteers (six female and 4 male) aged between 21 and 35 years was supplemented with 6 g/day of n-3 polyunsaturated fatty acids [3.6 g of eicosapentaenoic acid (EPA) and 2.4 g of docosahexaenoic acid (DHA)] for six weeks. Supine arterial blood pressure (BP) and heart rate (HR), renal hemodynamics, renal excretory function and urinary excretion of PGE2 and PGE3 were determined before and at the end of the fish oil supplementation period. No changes could be observed in BP and HR while renal plasma flow (RPF), determined as the clearance of PAH, significantly increased from 559 +/- 44 to 738 +/- 47 ml/min (P less than 0.001) with the fish oil supplements. This was associated with a decrease in renal vascular resistance from (8.11 +/- 0.54).10(-2) to (6.37 +/- 0.38).10(-2) mm Hg.min.ml-1 (P less than 0.01). Glomerular filtration rate (GFR), determined as the clearance of inulin, increased from 97 +/- 3 to 107 +/- 3 ml/min (P less than 0.01), resulting in a decrease in filtration fraction from an average of 0.19 +/- 0.01 to 0.15 +/- 0.01 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Acute purulent parotitis as a sequela of alkylphosphate (E 605) poisoning].
Acute suppurative parotitis is a possible consequence of poisoning by organophosphates (E 605). The endogenous accumulation of acetylcholine results--as in the acute pancreatitis caused by poisoning with organophosphates--in massive hyperemia and an increased secretory activity with leakage of saliva into the tissue, in an activation of the kallikrein-kinin system, the phospholipase A2, and, ultimately, in toxic tissue lesions caused by lysolecithin and the superoxide-radical anion. In spite of antibiotic therapy this is followed by bacterial inflammation. Treatment consists in the administration of aprotinin (Trasylol) and corticosteroids. In the case of abscess formation surgical drainage is necessary.
Acute Disease↗
Baroreceptor activity in man during administration of the calcium channel blocker felodipine.
The mechanisms responsible for the resetting of the baroreceptor reflex during long-term administration of 1,4 dihydropyridine calcium channel blockers are incompletely understood. The present study investigated the effect of 10 mg per day of felodipine on arterial blood pressure (BP), heart rate (HR), urinary norepinephrine, and cardiac beta-1-receptor sensitivity in 10 healthy volunteers. Blood pressure heart rate and urinary norepinephrine were determined during control and on days 1,4, and 14 of felodipine administration. Dose response curves of intravenous bolus injections of isoproterenol were performed on the same days to measure cardiac beta-1-receptor sensitivity. Felodipine significantly reduced the blood pressure from 131 +/- 6/74 +/- 3 mm Hg (mean +/- s.e.m.) to 123 +/- 6/65 +/- 2 mm Hg on day 1 (p less than 0.01). The blood pressure remained decreased during the entire protocol. The initial increase in the heart rate (62 +/- 5 to 67 +/- 4 min-1) remained elevated on day 4 and returned within the control range by day 14 (63 +/- 4 min-1) in spite of unchanged felodipine plasma levels (1.71 +/- 1.13 ng/ml (day 1) and 1.66 +/- 0.66 ng/ml (day 14). Urinary norepinephrine rose significantly with short-term felodipine administration (62 +/- 12 versus 50 +/- 6 micrograms/24 h; p less than 0.01). With long-term felodipine administration this value returned to pretreatment levels (55 +/- 12 micrograms/24 h). Cardiac beta-1-receptor sensitivity was not changed at any point of the protocol.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Fish oil and baroreceptor function in man.
The present study was designed to investigate the effects of dietary fish oil supplements on blood pressure, the pressor response to norepinephrine, and sensitivity of the arterial baroreceptor reflex. 10 normotensive volunteers (six female and 4 male) aged between 21 and 35 years were given 6 g/day of n-3 polyunsaturated fatty acids (3.6 g of eicosapentaenoic acid and 2.4 g of docosahexaenoic acid) during six weeks in addition to their usual diet. Resting blood pressure (BP), blood pressure response to exogenous norepinephrine (NE), and changes in heart rate (HR) associated with the blood pressure increase during NE infusion were determined before and at the end of the fish oil supplementation period. No changes in BP could be observed following the n-3 fatty acid supplements as compared to control values (110.7 +/- 2.4/63.5 +/- 2.9 mmHg vs. 110.6 +/- 1.9/60.1 +/- 1.3 mmHg). Blood pressure values during infusion of 0.1 micrograms/kg body weight of NE were 119.8 +/- 2.4/67.4 +/- 1.7 mmHg before the fish oil supplementation period and were also unchanged (119.9 +/- 2.0/70.5 +/- 1.9 mmHG) after the fish oil diet. HR during NE infusion was significantly (p less than 0.01) more suppressed after the fish oil supplementation period. During control, HR decreased in parallel with the rise in blood pressure from 69.2 +/- 2.8 min-1 to 63.9 +/- 2.4 min-1 (difference of 5.3 +/- 0.5 min-1), while after the fish oil supplementation HR fell from 68.1 +/- 3.5 min-1 to 56.2 +/- 2.6 min-1 (difference of 11.9 +/- 1.5 min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Dietary fat, hypertension, atherosclerosis.
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Animals↗
[The role of diuretics in the treatment of chronic heart failure].
Altered renal function with renal NaCl-retention can be observed early in the course of congestive heart failure. The afferent pathway of this altered regulation involves changes occurring in the high pressure system as a consequence of foreward failure such as an increase in baroreceptor reflex activity. Efferent pathways may include the renin-angiotensin-aldosterone system, the sympathetic nervous system, prostaglandins, dopamine, ANF, and AVP. At present, the relative importance of these systems in mediating renal NaCl-retention in heart failure is still unclear. Expansion of the extracellular fluid volume as a consequence of renal NaCl-retention may, at least acutely, compensate for compromised myocardial function via the Frank-Starling mechanism. As a consequence of volume expansion, chronically increased cardiac preload and possibly afterload may however even aggravate cardiac failure. Diuretics may therefore induce variable effects in patients with congestive heart failure. Acutely, they may ameliorate symptoms of congestion in spite of the possibility of a further decrease in cardiac index. Chronically, they may reduce cardiac pre- and afterload. Through a variety of mechanisms, they may therefore increase cardiac performance in spite of a fall in filling pressures.
Diuretics↗
Pseudohypertension in hypertensive patients on multiple drug therapy.
Differences in blood pressure between direct intra-arterial and indirect cuff measurements have been reported, especially in elderly patients. We investigated the incidence of pseudohypertension among hypertensives with a poor response to drug therapy. We studied 24 patients, aged between 18 and 65 years, whose blood pressure could not be normalized with a combination of at least two antihypertensive drugs. We found no difference in systolic blood pressure but diastolic blood pressure was significantly (P less than 0.001) lower when measured intra-arterially. The mean difference between the direct and the indirect blood pressure determination was 16.2 +/- 1.5 mmHg (s.e.m.), and the range was 2.3-39.6 mmHg. Age, duration of hypertension and left ventricular hypertrophy was not correlated with the incidence and extent of pseudohypertension. We conclude that in hypertensives with a poor response to drug therapy, blood pressure measurements should be taken intra-arterially in order to avoid the hazards of overtreatment.
Adolescent↗
Dietary linoleic acid deprivation: an experimental model of salt-sensitive hypertension.
The present study investigates arterial blood pressure (BP), renal arachidonic acid cyclooxygenase metabolism and excretory function in rats during dietary linoleic acid deprivation and a concomitant low and high NaCl-intake. Four groups of animals were fed isocaloric diets containing 10 energy (en) % saturated fat and either 5 en % linoleic acid (groups I and III) or 5 en % oleic acid (groups II and IV) over six weeks. In addition, groups I and II received a chronic high intake of sodium (5.4 mmol/24 h) while groups III and IV were NaCl-restricted (average NaCl intake of 0.7 mumol/24 h). Systolic BP significantly increased from 97.0 +/- 1.7 to 112.0 +/- 2.2 mmHg (p less than 0.01) in the salt loaded group II fed the diet deficient in linoleic acid and remained unchanged in the three other groups. Renal cyclooxygenase metabolism was significantly stimulated by sodium restriction and suppressed following dietary linoleic acid deprivation. During infusion of 0.45% saline to a stable increase in body weight of 10%, animals in the linoleic acid deprived groups II and IV excreted significantly less sodium, chloride, and potassium than animals in groups I and III. This impairment in renal excretory function occurred without concomitant changes in RPF, GFR, or UPhos V. It was associated, however, with marked decreases in fractional free water excretion (CH2O/GFR), distal delivery of solute [(CH2O + CCl)/GFR] and with an increase in "distal fractional chloride absorption" [CH2O/(CH2O + CCl)]. Furthermore, linoleic acid deprivation was associated with a significantly enhanced papillary osmolality and papillary sodium, chloride, and potassium concentrations in group II animals as compared to group I.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Hemodynamic effect of unsaturated fatty acids. Do fish oils have an antihypertensive effect?].
While there is still uncertainty about a possible blood pressure lowering effect of omega-6 fatty acids (vegetable oil) in man, a number of reports have described cardiovascular effects of an increased intake of omega-3 fatty acids (fish oil). In normotensive volunteers, unchanged or mildly decreased arterial blood pressure, a decrease in the response to exogenous vasopressors, especially noradrenaline, a rise in renal blood flow, and increased sensitivity of the arterial baroreflex system have been reported. In all studies involving patients with essential hypertension reported to date, omega-3 fatty acids have been shown to decrease arterial blood pressure. So far little is known about the dose-response relationship of this blood pressure-lowering effect. In the short-term studies available to date doses of more than 5 g/day of omega-3 fatty acids were necessary to effectively lower blood pressure. At present, the mechanism of the cardiovascular effects of fish oil is also unknown.
Blood Pressure↗
[Drug therapy of arterial hypertension. From graduated therapy to the individualized treatment concept].
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Antihypertensive Agents↗
Assessment of beta-blocking activity of low-dose bupranolol.
In the present study an investigation was made on the pharmacodynamic effect of the beta-blocking agent bupranolol in the low-dose range. Bupranolol is usually given in doses of 100 mg twice daily in the treatment of hypertension, however the dose range between 20 and 100 mg was studied using graded isoproterenol injections in healthy volunteers. A significant beta-1-blocking activity was observed for the 20 mg dose already. This effect was reduced after a treatment of 10 days. The effect increased with the higher doses, there might be a linear correlation between the logarithm of the dose and the reduction of the tachycardia after the isoproterenol injections in the low-dose range. It was concluded that using the safe and sensitive isoproterenol injection method, the clinical effect of very low doses of bupranolol may be demonstrated. The low dose might be useful to reduce the reflex tachycardia seen in the treatment of hypertension with vasodilating drugs.
Adrenergic beta-Antagonists↗
[Mechanism and significance of arteriolar media hypertrophy/ hyperplasia in arterial hypertension. Role of the Na+/H+ antiport].
The most common haemodynamic abnormality in human essential hypertension is an increase in systemic vascular resistance. Morphologic substrate for increased flow resistance is a narrowing of the lumen of arteriolar resistance vessels. During the course of essential hypertension, this is associated with an increase in wall (mainly media) thickness due to hypertrophy and hyperplasia of vascular smooth muscle cells. In contrast to concepts interpreting media thickening strictly as structural adaptation to increased perfusion pressure, various lines of evidence also point to pressure independent factors. In this context, extracellular factors such as "growth factors" as well as alterations in the activity of intracellular messenger systems must be considered. Recent studies suggest that substances generally known to act as vasoconstrictors such as angiotensin II, noradrenaline and arginine-vasopressin may also stimulate vascular smooth muscle cell growth and proliferation. Intracellular messenger systems with possible significance in the response to trophins and/or mitogens of vascular smooth muscle cells are phospholipase C, protein kinase C and the Na+/H+-antiport. These systems have been demonstrated to be altered in hypertension supporting the concept that one endogenous factor in human essential hypertension with pathophysiological significance, at least in a subgroup of patients, may be an enhanced reactivity of vascular smooth muscle cells to trophic and mitogenic stimuli. In this context, intracellular messenger systems such as phospholipase C, protein kinase C and/or the Na+/H+-antiport may play an important pathophysiological role.
Antiporters↗
Purified verotoxins of Escherichia coli O157:H7 decrease prostacyclin synthesis by endothelial cells.
Two immunologically distinct verotoxins purified from Escherichia coli C600, lysogenized with distinct temperate phages from E. coli strain 933 of serotype O157:H7, were compared by SDS-PAGE and different biological assays. The two toxins termed verotoxin 1 (VT1) and verotoxin 2 (VT2) differing in molecular weight exhibited similar biological activities. Both preparations were toxic for HeLa cells and lethal for mice. Epidemiological evidence of verotoxinogenesis in some cases of hemolytic-uremic syndrome (HUS) and the recent observations of inadequate prostacyclin production by endothelial cells associated with HUS prompted us to study the effect of purified verotoxins on prostacyclin synthesis in rat aortic tissue. Our results demonstrate a significant reduction of prostacyclin by both toxins at picomolar levels. The suppression of prostacyclin release by a lower concentration of VT2 as compared with VT1 reflects the relative potencies of these toxins in HeLa cell toxicity and mouse lethality. The results suggest an effect of verotoxins on endothelial cells and support the concept of these toxins as virulence factors in E. coli.
Animals↗
[Elevated plasma levels and heterogeneity of human atrial natriuretic peptide in patients with progressive chronic renal failure].
The role of human atrial natriuretic peptide (alpha-hANP) in chronic blood pressure (BP) and extracellular fluid volume (ECFV) regulation remains elusive. Hence, the role of alpha-hANP in chronic renal failure is of particular interest since in this pathological condition: (1) increased sodium and water retention plays a major pathogenetic role in the development of hypertension and (2) altered secretion and/or metabolism of alpha-hANP may contribute to fluid volume and BP regulation. To evaluate the relationship between the degree of renal insufficiency, BP and circulating alpha-hANP, we determined plasma alpha-hANP concentrations by radioimmunoassay in 16 nondialyzed patients with progressive chronic renal failure (CRF) of various degrees; subsequently analysis of potential molecular heterogeneity of immunoreactive (ir) ANP was performed by means of gel permeation of plasma extracts from patients with CRF without concomitant hypertension. Serum creatinine concentrations ranged from 127 to 1187 (435 +/- 76) mumol/l, systolic BP from 135 to 200 (158 +/- 4) and diastolic BP from 80 to 110 (94 +/- 2) mmHg, respectively. Plasma alpha-hANP concentrations ranged from 5 to 75 (23 +/- 4) pmol/l which was thus significantly higher as compared to 9 +/- 2 pmol/l found in healthy volunteers (p less than 0.05). A highly significant linear correlation between plasma alpha-hANP and serum creatinine concentrations (r = 0.92; p less than 0.01) was observed; a weaker correlation was found between mean arterial pressure and alpha-hANP (r = 0.66) and serum creatinine concentration (r = 0.59), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗