Oxidation of low-density lipoprotein increases vasoconstriction in vitro.
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Biomedical subjects
Publications and source records attributed to B Weisser.
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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.
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.
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)
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.
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)
Until a few years ago, only casual blood pressure measurements were used in the diagnosis and treatment of arterial hypertension in clinical practice and in pharmacological studies. The development of portable lightweight devices for 24-h ambulatory blood pressure measurement has proved a substantial step towards reducing the potential pitfalls of casual blood pressure measurements. Ambulatory monitoring of blood pressure can improve pharmacological trials by excluding patients in whom blood pressure is elevated only in the clinic environment, and by increasing the accuracy and reproducibility of blood pressure values. Twenty-four-hour blood pressure measurement has great advantages for trials investigating the time-course of a particular drug, since the 24-h blood pressure rhythm is fully monitored. However, internationally accepted normal values for 24-h blood pressure measurements are required, and the interpretation of results obtained with this method needs to be standardized before the technique can be routinely used in antihypertensive drug trials.
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)
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.
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.
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.
The problems involved in treating psychogenic movement disorders in mentally retarded persons are pointed out. A psychoanalytic approach is doomed to failure because of the mental handicap. The authors report positive therapeutic results with a 17-year-old girl who had a severe hysterical movement disorder including sudden falls and a grotesque gait. Successful behavior therapy with this patient supports the hypothesis that conditioning was the chief factor in the maintenance of the symptoms and indicates that even severe mental retardation does not necessarily imply that there will be resistance to extinction. The individuals of greatest significance to the patient should, in the author's view, play an important part in the treatment program.
Various lipid-lowering drugs have been shown to reduce serum cholesterol and serum triglycerides effectively. In view of trials indicating that lipid-lowering drugs may reduce cardiac morbidity and mortality but not the overall mortality in the study group, increased attention must be focused on potential harmful side effects during treatment with these agents. The adverse effects of many of the principal drugs in this category are discussed. Gastrointestinal symptoms, usually self-limited and reversible, are the most common side effects. Potential harmful adverse effects include drug interactions (cholestyramine), myopathy and hepatic injury (HMG-CoA reductase inhibitors), and increased gallstone formation and ventricular arrhythmias (clofibrate). Not all lipid-lowering drugs have been studied adequately on a long term basis, so that medications given for an indefinite period must be reevaluated frequently. However, there are several agents that lower serum lipid levels effectively and that have been used for more than 20 years without serious side effects.