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Biomedical subjects

K H Rahn

Publications and source records attributed to K H Rahn.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group.

BACKGROUND: Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension. METHODS: 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo. FINDINGS: Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001). INTERPRETATION: Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.

Aged↗
PubMed1998

[The Hypertension Optimal Treatment (HOT) study: results of 12-month therapy related to age].

BACKGROUND AND OBJECTIVE: The prospective, randomized multicentre HOT study (Hypertension Optimal Treatment) is at present being undertaken in 26 countries. The cardinal questions to be answered were: (1) the relationship between three targeted diastolic pressures (< or = 90, < or = 85 and < or = 80 mm Hg, respectively) and cardiovascular morbidity and mortality rates among hypertensives; and (2) the effect of low dosage aspirin (75 mg daily) on morbidity and mortality rates, compared with a placebo. PATIENTS AND METHODS: A total of 19,193 patients (9056 women, 10,137 men; age range 50-80 years) with a diastolic blood pressure of > or = 100 to < or = 115 mm Hg were randomized. Antihypertensive treatment was begun with the calcium-channel blocker felodipine (5 mg once daily; step 1). When the target could not be reached at this dosage, an angiotensin-converting enzyme inhibitor (ACEI) or beta-receptor blocker was added (stage two), after which felodipine, 10 mg daily, could be given, if necessary (step 3). Any necessary changes in dosage (step 4) were made according to a prescribed plan. As fifth and final step a diuretic could be additionally administered. One-year results are now available for all patients and reported here. Results of older patients (> or = 65 years, n = 6113) were compared to those of younger patients (< 65 years, n = 13,080). RESULTS: Average diastolic pressure in the previously < or = 90 mm Hg group had been reduced to 86 mm Hg, in the < or = 85 group to 83 mm Hg, and in the < or 80 mm Hg group to 81 mm Hg. The percentage proportion of patients in whom the targeted pressures had been reached after 12 months of treatment were: 84% for the < 90 mm Hg group, 72% in the < 85 mm Hg group and 57% in the < 80 mm Hg group. In a subgroup of elderly patients (> 65 years, n = 6113) the corresponding percentage proportions were higher: 86%, 76% and 61%. Side effects were noted only rarely, despite the intensive treatment (> 65 years and < 65 years): ankle oedema in 2.6% and 3.0%; and cough in 1.3 and 0.8%, an overall incidence of > or = 1%. The same treatment (with felodipine) was still being given after one year to 88% of all patients. CONCLUSION: These results after one year indicate that most patients well tolerate consistent blood pressure reduction. This raises the hope that the primary questions of the study can be answered.

Adrenergic beta-Antagonists↗
PubMed1998

Decreased membrane Mg2+ concentrations in a subgroup of hypertensives: membrane model for the pathogenesis of primary hypertension.

Intracellular Mg2+ measurements were performed in erythrocyte membranes of 18 untreated normotensive and 19 untreated essential hypertensive patients. Mg2+ concentrations were determined by atomic absorption spectroscopy using a Video 12 apparatus. The results show that in patients with essential hypertension total Mg2+ content in erythrocyte membranes was significantly decreased as compared with the control group (0.28 +/-0.05 v 0.52+/-0.15 mmol/g membrane protein; mean+/-SD, P < .001). Additionally, plasma and free intracellular Mg2+ content of lymphocytes and platelets showed no significant difference in normotensives and hypertensives. Lowered total membrane Mg2+ concentrations in a subgroup of primary hypertensives may contribute to the development of this disorder, perhaps due to different buffering or membrane transport systems.

Adult↗
PubMed1998

Renal function in treated and untreated hypertension.

There is now increasing evidence that essential hypertension is a serious risk factor for renal insufficiency. It has been known for many years that malignant essential hypertension rapidly causes deterioration of kidney function. This can be prevented by treatment with anti-hypertensive drugs. Mild-to-moderate essential hypertension causes significant renal function impairment only after a number of years. There are now data suggesting that the decline of renal function caused by mild-to-moderate essential hypertension can be prevented by anti-hypertensive treatment. In recent years, it has been demonstrated that anti-hypertensive drugs have a beneficial effect on the progression of renal insufficiency in patients with diabetic nephropathy and in chronic glomerulonephritis. In these situations, ACE inhibitors appear to be superior to other classes of anti-hypertensive drugs.

Aged↗
PubMed1998

A longitudinal study of vessel wall properties in normotensive and hypertensive renal transplant recipients.

The mechanisms responsible for reduced arterial distensibility in renal transplant recipients remain to be evaluated. The present longitudinal study was aimed to evaluate the effect of hypertension on the evolution of vessel wall properties in renal transplant recipients. The mechanical properties of the common carotid artery were determined in 24 normotensive and 24 treated hypertensive renal transplant recipients 6-12 weeks after transplantation. The measurements were repeated after 2 years. Arterial distension was determined by using a multigate pulsed Doppler system, blood pressure (BP) was measured by a mercury sphygmomanometer. BP was 127 +/- 3/80 +/- 2 mm Hg at entry and 133 +/- 3/82 +/- 2 mm Hg after 2 years in the normotensive group, 146 +/- 4/90 +/- 3 mm Hg at entry and 145 +/- 3/87 +/- 2 mm Hg after 2 years in the hypertensive group (P < 0.01, normotensives vs hypertensives). The distensibility coefficient (DC) decreased significantly after 2 years in the hypertensive group (DC 18.3 +/- 1.3 10(-3)/kPa before, 15.1 +/- 1.2 10(-3)/kPa after 2 years, P < 0.05) whereas no significant change was observed in the normotensive group (DC 19.0 +/- 1.4 10(-3)/kPa before, DC 17.8 +/- 1.3 10(-3)/kPa after 2 years, NS). There was a significant correlation between the change of the distensibility coefficient after 2 years and mean arterial pressure (n = 48, r = 0.42, P < 0.01). The results show that the decrease of arterial distensibility after 2 years is accelerated in hypertensive renal transplant recipients despite effective anti-hypertensive treatment. Since BP levels were not different at entry into the study and after 2 years, differences in distending pressure along cannot explain the more pronounced decrease of arterial distensibility over time in hypertensive renal transplant recipients.

Adult↗
PubMed1998

Increased Na+ and decreased Mg2+ intracellular concentrations in vascular smooth muscle cells from spontaneously hypertensive rats.

1. Although in blood cells decreased magnesium concentrations and increased sodium concentrations in essential hypertension have often been described, only sparse data exist on cellular magnesium or sodium content and exchange in vascular smooth muscle cells.2. Therefore in aortic smooth muscle cells from 10 spontaneously hypertensive rats (SHR) of the Münster strain and 10 normotensive Wistar-Kyoto rats (WKY) aged 3 and 8-10 months, the intracellular magnesium and sodium content was measured.3.Electron-probe X-ray microanalysis was used to determine intracellular Mg2+ and Na+ concentrations in aortic cryosections 3 micron thick. The Mg2+ content was 47+/-13 mmol/kg dry weight in SHR versus 48+/-19 mmol/kg dry weight in WKY aged 3 months, and 37+/-6 mmol/kg dry weight in SHR versus 47+/-4 mmol/kg dry weight in WKY aged 8-10 months (P<0. 05). Vascular smooth muscle Na+ content was 283+/-59 mmol/kg dry weight in WKY and 402+/-123 mmol/kg dry weight in SHR aged 3 months (P<0.05), and 289+/-17 mmol/kg dry weight in WKY versus 548+/-39 mmol/kg dry weight in SHR aged 8-10 months (P<0.05).4. Aortic smooth muscle cells from SHR are characterized by a markedly lower intracellular Mg2+ content in 8-10-month-old animals and increased Na+ concentrations compared with normotensive cells in 3- and 8-10-month-old rats. The results may be due to genetically determined disturbances in transmembrane Mg2+ and Na+ transport. Cellular magnesium and sodium handling may be disturbed in SHR aortic smooth muscle as it is in hypertensive blood cells. In addition, it is concluded that vascular smooth muscle cell Mg2+-Na+ exchanger can be altered in a subgroup of SHR.

Animals↗
PubMed1998

Effect of hyperparathyroidism on arterial distensibility in renal transplant recipients.

BACKGROUND: The cushioning function of the arterial system is altered in patients with end-stage renal failure. The role of hyperparathyroidism for the altered vessel wall properties of large arteries not known. METHODS: To exclude the confounding effects of fluid volume changes and hypercirculation as well as uremic toxicity on vessel wall properties from those of hyperparathyroidism, the present study was conducted in 54 normotensive renal transplant recipients with good graft function, three to six months after transplantation. The vessel wall properties of the common carotid artery were investigated in 32 of them, who had increased plasma intact parathyroid hormone (iPTH) levels (136 +/- 12 ng/liter, SEM), and compared to those of 22 control recipients of same age with normal plasma iPTH levels (34 +/- 4 ng/liter). Arterial distension was measured by Doppler analysis of the vessel wall movements, blood pressure was determined by sphygmomanometry. RESULTS: Blood pressure was 140 +/- 3/85 +/- 2 mm Hg in renal transplant recipients with hyperparathyroidism, 135 +/- 3/83 +/- 1 mm Hg in patients with normal plasma iPTH levels (NS). There was no difference in enddiastolic diameter of the common carotid artery (7.4 +/- 0.2 mm) in renal transplant recipients with hyperparathyroidism as compared with the control patients (7.3 +/- 0.2 mm; NS). Renal transplant recipients with hyperparathyroidism had a lower distension (389 +/- 27 microns vs. 486 +/- 28 microns, P < 0.05) and distensibility coefficient of the common carotid artery (15.1 +/- 1.1 10(-3)/kPa vs. DC 19.0 +/- 1.0 10(-3)/kPa, P < 0.001) when compared with the control patients. Multiple regression analysis showed that the distensibility coefficient of the common carotid artery was negatively correlated with age (P < 0.001), mean arterial blood pressure (P < 0.05) and plasma iPTH levels (P < 0.05). The effects of plasma iPTH levels were not related to serum calcium concentrations or to differences in the enddiastolic diameter of the common carotid artery. CONCLUSIONS: The data suggest that secondary hyperparathyroidism can affect the cushioning function of larger arteries in patients with end-stage renal failure independently of high blood pressure.

Adult↗
PubMed1998

Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis.

BACKGROUND: The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls. DESIGN: The European Lacidipine Study on Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multinational trial comparing effects of 4-year treatment based on the long-acting, highly lipophilic calcium antagonist lacidipine with those of treatment based on the beta-blocker atenolol on the development of carotid artery wall alterations in patients (aged 45-75 years) with mild-to-moderate hypertension (systolic blood pressure 150-210 mmHg and diastolic blood pressure 95-115 mmHg). While the intervention study is progressing, this article summarizes baseline data obtained from the whole cohort of 2259 patients randomly allocated to treatment. METHODS: Baseline ultrasound data were obtained from two replicate examinations performed shortly before random allocation to treatment by certified sonographers at 23 referral centres and read at the ultrasound coordinating centre at the Wake Forest University School of Medicine. Intima-media thickness was measured at up to 12 different sites in the carotid artery tree and expressed as the mean of the maxima at these sites (Mmax), the mean of the maxima at four sites in the distal common carotid artery and bifurcation (CBMmax) and the maximum intima-media thickness (Tmax). Baseline demographic and clinical measurements were performed by investigators in 410 peripheral clinical units and 24 h ambulatory blood pressure monitorings read and validated by members of a centralized unit at the University of Milan. The statistical analysis centre at the Technische Universität München received and analysed all baseline data, by calculating means +/- SD, medians and ranges and performing correlation (Spearman correlation coefficients) and multiple regression analyses. RESULTS: Prevalence of carotid artery wall alterations among the hypertensive patients randomly allocated to treatment in the ELSA was very high: 82% had Tmax > or = 1.3 mm ('plaques' according to protocol) and 17% had Tmax > or = 1.0 and < 1.3 mm ('thickening'), with a median of two plaques per patient. We found significant correlations between ultrasound measurements and the following demographic and clinical variables: age, sex, systolic blood pressure and pulse pressure (both clinic and ambulatory), concentrations of total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides, smoking habit and duration of hypertension. We found no significant correlation to diastolic blood pressure and glucose concentration. A multiple regression analysis indicated significant variables in the following rank order: age, 24 h ambulatory pulse pressure, sex, low-density lipoprotein cholesterol concentration, triglyceride concentration, smoking and clinic systolic blood pressure. CONCLUSIONS: Analysis of baseline data from the ELSA has shown that there is an extremely marked prevalence of carotid artery wall alterations among mild-to-moderate, middle-aged hypertensive patients. In addition to age, systolic blood pressure and pulse pressure, particularly if they are accurately measured by ambulatory monitoring, play a major role, somewhat greater than those of sex, low-density lipoprotein cholesterol concentration and smoking, in influencing intima-media thickness.

Adrenergic beta-Antagonists↗
PubMed1998

Plasma and membrane Ca2+ and Mg2+ concentrations in normal pregnancy and in preeclampsia.

OBJECTIVE: Changes in intracellular Ca2+ and Mg2+ concentrations seem to be involved in the pathogenesis of preeclampsia, whereas the role of cell membranes has not been studied in detail yet. To investigate the changes in Ca2+ and Mg2+ metabolism in normal pregnancy and preeclampsia, plasma and membrane Ca2+ and Mg2+ concentrations were determined in a clinical study as compared to healthy subjects. STUDY DESIGN: 25 healthy female subjects, 22 untreated healthy pregnant and 20 preeclamptic women were investigated. In each patient, plasma and membrane Ca2+ and Mg2+ content were measured. Ca2+ and Mg2+ concentrations were measured by atomic absorption spectroscopy. Erythrocyte membranes were chosen for membranous Ca2+ and Mg2+ determination. RESULTS: Plasma Mg2+ concentrations were significantly lowered in the healthy pregnant group and the preeclamptic group as compared to controls (p < 0.0001). In erythrocyte membranes, Mg2+ content was found significantly decreased in the preeclamptic women as compared to healthy subjects (p < 0.001). In plasma Ca2+ concentrations there was a significant decrease in the preeclamptic group as compared to controls or healthy pregnant women (p < 0.05). Membranous Ca2+ content was significantly increased in the preeclamptic group versus controls or healthy pregnant women (p < 0.001). CONCLUSION: Lowered plasma and membrane Mg2+ concentrations in preeclampsia may contribute to the development of hypertension in pregnancy. Additionally, a disturbed Ca2+ homeostasis is observed in preeclampsia.

Blood Pressure↗
PubMed1998

Effects of diadenosine polyphosphates on the intracellular Ca2+ concentration in endothelial cells.

Diadenosine polyphosphates have differential hemodynamic effects. The role of the endothelium in the vascular effects of these agonists is still unclear. Primary cultures of rat aortal endothelial cells and Ea.hy 926 cells (a continuous endothelial cell line) were used to investigate the effects of Ap3A-Ap6A, adenosine triphosphate (ATP), and for comparison, arginine vasopressin (AVP) and angiotensin II (A II) on the intracellular Ca2+ concentration, [Ca2+]i. Fura-2 was used as Ca2+ indicator. In rat aortal endothelial cells, ATP and Ap4A concentration dependently increased [Ca2+]i with an initial peak followed by an elevated plateau. The half-maximal effects were reached at approximately 7 micromol/l for ATP and at approximately 10 micromol/l for Ap4A. The maximal peak effects at 100 micromol/l were 1,035 +/- 413 nmol/l (n = 3) and 437 +/- 271 nmol/l (n = 8) for ATP and Ap4A, respectively. At 100 micromol/l Ap3A and Ap6A slightly increased [Ca2+]i, while Ap5A had no significant effect. The known endothelial agonists AVP (100 nmol/l) and A II (10 nmol/l) increased [Ca2+]i initially by 1,549 +/- 913 nmol/l (n = 7) and 209 +/- 45 nmol/l (n = 9), respectively. In Ea.hy 926 cells an increase in [Ca2+]i was obtained only with ATP (10 micromol/l) and with Ap4A (100 micromol/l). Ap3A, Ap5A, and Ap6A (each 100 micromol/l) and also AVP (100 nmol/l) and A II (10 nmol/l) had no significant effects in these cells. These results show that a considerable increase in [Ca2+]i in endothelial cells can only be induced by Ap4A among the diadenosine polyphosphates, indicating that the vasoactive effects of only this polyphosphate could at least partly be mediated via Ca2+-dependent mechanisms in endothelial cells, comparable to the known effects of AVP, A II, and ATP. The fact that A II and AVP did not influence [Ca2+]i in Ea.hy 926 cells is probably due to the loss of the respective receptors in this cell line.

Adenosine Triphosphate↗
PubMed1998

Effects of diadenosine polyphosphates on systemic and regional hemodynamics in anesthetized rats.

Diadenosine polyphosphates (Ap4A, Ap5A, Ap6A) induce vasodilatation or vasoconstriction in various isolated vessels and influence central and peripheral hemodynamics. The influence of diadenosine polyphosphates on hemodynamics was studied in anesthetized rats in vivo. Mean arterial blood pressure (MABP) and heart rate (HR) measured in the carotid artery decreased with Ap4A, Ap5A, and Ap6A. Renal blood flow (RBF), femoral blood flow (FBF) and cardiac output (CO) were evaluated by an ultrasonic transit-time method. Renal superficial blood flow (RSBF) was measured by laser Doppler flowmetry. CO, RBF and RSBF were decreased initially by all three diadenosine polyphosphates. FBF was also slightly decreased. Total peripheral (TPR), renal (RVR) and femoral (FVR) vascular resistances were calculated. TPR was transiently increased by the dinucleotides following by a decrease. RVR and, to a lesser extent, FVR were also increased. These data show that diadenosine polyphosphates have effects on both the heart and the peripheral blood vessels. The effects on the heart and MABP were dominated by bradycardia and hypotension. In the kidney, diadenosine polyphosphates induced a predominant vascoconstriction. The effects on skeletal muscle blood flow were much smaller. Thus, the three diadenosine polyphosphates studied differ in the effects on heart and peripheral vessels.

Animals↗
PubMed1997

Decreased cellular Mg2+ concentrations in a subgroup of hypertensives--cell models for the pathogenesis of primary hypertension.

A new method to determine total Mg2+ content in lymphocytes was developed, offering advantages for routine measurements as compared to fluorescence methods. Intracellular Mg2+ measurements were performed in lymphocytes of 18 untreated normotensive and 19 untreated essential hypertensive patients. Mg2+ content was referred to lymphocytic protein, which was determined according to Bradford's method. Mg2+ measurements were performed by atomic absorption spectroscopy using a Video 12 apparatus from Thermo Electron Instrumentation Laboratory, Andover, MA, USA. The results show that in patients with essential hypertension, total intralymphocytic Mg2+ content is significantly lower (0.07 +/- 0.05 mmol/g lymphocytic protein, mean +/- s.d.) as compared to controls (0.11 +/- 0.04 mmol/g lymphocytic protein, mean +/- s.d., P < 0.05). Free intracellular Mg2+ content was measured in lymphocytes by the fluorescent indicator mag-fura-II, showing no significant difference in normotensives and hypertensives (0.30 +/- 0.16 vs 0.38 +/- 0.17 mmol/l). In platelets free intracellular Mg2+ concentrations were not found of significant difference in normotensive and hypertensive patients (0.52 +/- 0.23 vs 0.47 +/- 0.27 mmol/l) using mag-fura-II. In plasma Mg2+ concentrations there was no significant difference in the normotensive and hypertensive group (0.92 +/- 0.07 vs 0.88 to 0.07 mmol/l). There was no correlation between plasma, free or total cellular magnesium concentrations in each group. Furthermore this method also seems suitable for routine measurements of total intracellular Mg2+ concentrations in even larger groups of patients in comparison with fluorescent indicator measurements like mag-fura-II. Lowered total intracellular Mg2+ concentrations in a subgroup of primary hypertension may contribute to the development of this disorder, perhaps due to different buffering systems.

Adult↗