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Whether endothelial dysfunction in essential hypertension is a cause or a consequence of structural vessel wall alterations is not known. The purpose of the present study was to compare flow-mediated vasodilation and mechanical vessel wall properties of large arteries between never treated mild essential hypertensive patients with normal intima-media thickness (IMT) and those exhibiting intima-media thickening. We measured brachial and carotid artery diameter and distension by Doppler frequency analysis of vessel wall movements in M-mode in ten essential hypertensive patients with normal carotid artery IMT (HYP1), in ten patients with increased IMT (HYP2), and in 13 normotensive control subjects (CON). Thereafter, we measured changes in brachial artery (BA) diameters during distal reactive hyperemia after 4 min of forearm occlusion. Nitroglycerin-mediated vasodilation was measured to assess endothelium-independent vasodilation, and BA blood flow was estimated using a pulsed Doppler system. Intima-media thickness of the carotid arteries was examined by high resolution B-mode ultrasound. IMT was 0.66 +/- 0.02 mm in the HYP1 group, 0.84 +/- 0.03 mm in the HYP2 group (P < .01 v HYP1, P < .01 v CON), and 0.71 +/- 0.04 mm in the CON group. Forearm occlusion was reduced in both the HYP1 group (3.4% +/- 3.6%, P < .01 v CON) and the HYP2 group (6.4% +/- 1.5%, P < .05 v CON) when compared with the CON group (16.5% +/- 2.8%). Nitroglycerin-mediated vasodilation and BA blood flow were not different between study groups. BA distension (as well as carotid artery distension) was significantly lower in the HYP1 group (52 +/- 6 microm, P < .05 v CON), but not in the HYP2 group (72 +/- 10 microm) when compared with the CON group (88 +/- 13 microm). The data suggest that endothelial dysfunction and reduced distensibility of large arteries in patients with essential hypertension occur in the absence of structural vessel wall alterations.

There are now numerous studies demonstrating that essential hypertension is accompanied by sympathetic activation. Using drugs which block cardiac sympathetic effects, it could be shown that a noticeable fraction of subjects with borderline hypertension had an increased sympathetic drive. A meta-analysis of studies on plasma noradrenaline levels as an indirect marker of sympathetic tone reported that noradrenaline concentrations were significantly elevated in patients with essential hypertension as compared with normotensive control subjects. In addition, it could be shown that the rate of noradrenaline spillover from sympathetic nerve terminals was sometimes increased in essential hypertension, particularly in young hypertensive subjects. Additional data have emerged by direct measurement of sympathetic nerve traffic to skeletal muscle circulation using a microelectrode technique. Most studies using this method have demonstrated increased sympathetic nerve activity in patients with essential hypertension. In contrast, patients with secondary hypertension did not differ from normotensive subjects. Taken together, the data available at present show that sympathetic activation is a specific feature of essential hypertension and that it may play a pathogenetic role in this disease.

Whereas 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. Therefore in aortic smooth muscle cells from 10 spontaneously hypertensive rats (SHR) of the Münster strain and 10 normotensive Wistar-Kyoto rats (WKY) aged 8 to 10 months, the intracellular magnesium and sodium content was measured. Electron-probe X-ray microanalysis was used to determine intracellular Mg2+ and Na+ concentrations in aortic cryosections 3 microm thick. The magnesium ion content was 0.90 +/- 0.15 g/kg dry weight in SHR versus 1.15 +/- 0.10 g/kg dry weight in WKY (means +/- SD, P < .05). Vascular smooth muscle sodium ion content was 6.66 +/- 0.39 g/kg dry weight in WKY and 12.61 +/- 0.91 g/kg dry weight in SHR (P < .01). Aortic smooth muscle cells from SHR are characterized by markedly lowered intracellular magnesium ion content and increased sodium ion concentrations in animals 8 to 10 months old, compared with normotensive cells. The results may be due to genetically determined disturbances in transmembrane magnesium and sodium ion transport.

Background: Power spectral analysis of heart rate variability and arterial distensibility are non-invasive measures of cardiac autonomic modulation and mechanical vessel wall properties, respectively. The aim of the present study was to assess cardiac sympathovagal balance, carotid and brachial artery distensibility and a possible relation between these parameters in mildly hypertensive patients as compared to normotensive controls., Methods: Total power (TP, 0.01 to 0.5 Hz) and spectral components (low frequency 0.04-0.15 Hz, mainly sympathetic cardiac modulation; high frequency 0.15-0.4 Hz, mainly vagal cardiac modulation) and cardiac sympathovagal balance (LF/LH ratio) of short term heart rate variability (ECG-recording) were calculated in 15 untreated essential hypertensive patients (HYP) and 15 age- and sex-matched healthy controls (CON). Brachial and carotid artery distensibility coefficient (DC) was measured with a multigate doppler system (echo-tracking)., Results: TP (ms2 x 10(-3)) (11.2 +/- 0.8 vs 13.6 +/- 0.9, P < 0.03), LF/HF ratio (1.07 +/- 0.08 vs 0.75 +/- 0.07, P < 0.01) and HF (ms2 x 10(-3)/%) (0.7 +/- 0.1/49 +/- 2 vs 1.3 +/- 0.2/58 +/- 2, P < 0.01/P < 0.01) were significantly reduced in HYP compared to CON subjects. LF (ms2 x 10(-3)/%) was 0.7 +/- 0.1/50 +/- 2 vs 0.9 +/- 0.1/41 +/- 2, P = 0.16/P < 0.01. Carotid artery DC (15 +/- 2 vs 26 +/- 2, P < 0.001) and brachial artery DC (4.7 +/- 0.6 vs 9 +/- 1.0, P < 0.001) were significantly reduced in HYP. There was a significant correlation between carotid DC and LF/HF (rho = -0.41, P < 0.03)., Conclusion: The data shows reduced heart rate variability and altered cardiac sympathovagal balance as well as impaired arterial distensibility in untreated mildly hypertensive patients. The relative increase in sympathetic modulation and decreased carotid distensibility appear to be related.

Background: Alterations of large artery function and structure are frequently observed in renal allograft recipients. However, endothelial function has not yet been assessed in this population., Methods: Flow-mediated vasodilation is a useful index of endothelial function. We measured the diameter and distensibility of the brachial artery at rest using high-resolution ultrasound and Doppler frequency analysis of vessel wall movements in the M mode. Thereafter, changes in brachial artery diameter were measured during reactive hyperemia (after 4 min of forearm occlusion) in 16 cyclosporine-treated renal allograft recipients and 16 normal controls of similar age and sex ratio. Nitroglycerin-mediated vasodilation was measured to assess endothelium-independent vasodilation. Brachial artery blood pressure was measured using an automatic sphygmomanometer, and brachial artery flow was estimated using pulsed Doppler., Results: Distensibility was reduced in renal allograft recipients (5.31 +/- 0. 74 vs. 9.10 +/- 0.94 x 10-3/kPa, P = 0.003, mean +/- sem), while the brachial artery diameter at rest was higher (4.13 +/- 0.14 vs. 3.25 +/- 0.14 mm, P < 0.001). Flow-mediated vasodilation was significantly reduced in renal allograft recipients (0.13 +/- 0.08 vs. 0.60 +/- 0.08 mm or 3 +/- 2 vs. 19 +/- 3%, both P < 0.001). However, nitroglycerin-mediated vasodilation was similar in renal allograft recipients and controls (0.76 +/- 0.10 vs. 0.77 +/- 0.09 mm, NS, or 19 +/- 3 vs. 22 +/- 2%, NS). There were no significant differences in brachial artery flow at rest and during reactive hyperemia between both groups. The impairments of flow-mediated vasodilation and distensibility in renal allograft recipients remained significant after correction for serum cholesterol, creatinine, parathyroid hormone concentrations, end-diastolic diameter, as well as blood pressure levels, and were also present in eight renal allograft recipients not treated with cyclosporine. Flow-mediated vasodilation was not related to distensibility in either group., Conclusions: The results show impaired endothelial function and reduced brachial artery distensibility in renal allograft recipients. The impairments of flow-mediated vasodilation and distensibility are not attributable to a diminished brachial artery vasodilator capacity, because endothelium-independent vasodilation was preserved in renal allograft recipients.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to slow the progression of chronic renal failure. However, the value of ACE inhibitors for the treatment of hypertension in renal allograft recipients has not been established. ACE inhibitors dilate the efferent glomerular arteriole, an effect that may aggravate the decrease in glomerular filtration rate resulting from cyclosporine-induced vasoconstriction at the afferent glomerular arteriole. Therefore, the goal of this double-blind, randomized study was to compare the antihypertensive and renal effects of the ACE inhibitor quinapril with those of the beta-blocker atenolol in renal allograft recipients in whom hypertension developed 6 to 12 weeks after transplantation. All patients received cyclosporine as an immunosuppressant and had stable graft function (serum creatinine concentration, <220 micromol/L) at entry into the study. Twenty-nine patients who received quinapril (daily dose titrated between 2.5 and 20 mg) and 30 patients who received atenolol (daily dose titrated between 12.5 and 100 mg) completed the 24-month study. The two groups did not differ in age, sex ratio, height, and weight before entry into the study. Quinapril decreased diastolic blood pressure from 96+/-1 to 84+/-1 mm Hg (average throughout treatment period), and atenolol decreased diastolic blood pressure from 96+/-1 to 83+/-1 mm Hg. The serum creatinine concentration did not change significantly in either group after 24 months (129+/-8 micromol/L at entry and 148+/-19 micromol/L after 24 months in the quinapril group and 131+/-6 micromol/L at entry and 152+/-15 micromol/L after 24 months in the atenolol group; P=NS for both groups). After 24 months, the change in urinary albumin excretion from baseline was -10+/-15 mg/d in the quinapril group and 52+/-32 mg/d in the atenolol group (P=0.03). These results show that quinapril and atenolol are effective antihypertensive drugs when used after renal transplantation. Moreover, compared with atenolol, quinapril has no adverse effects on graft function. The relative reduction in albuminuria observed with quinapril as compared with atenolol could indicate a beneficial effect of quinapril on long-term graft function.

History and Clinical Findings: A 49-year-old, otherwise healthy woman had recurrent fever and lymphadenopathy with leukopenia for nineteen years. Her symptoms prompted successless antibiotic therapy and extensive evaluations of fever of unknown origin. At admission there were several enlarged cervical lymph nodes and subfebrile temperatures., Investigations: Neither laboratory findings nor imaging did show an infectious, rheumatologic or hematologic cause of her symptoms. Histopathological examination of an lymph node biopsy revealed histiocytic, necrotizing lymphadenitis (Kikuchi-Fusimoto disease) as the underlying disease., Treatment and Course: After spontaneous resolution without specific therapy the patient is now symptomless and well 9 months after diagnosis., Conclusion: Kikuchi-Fusimoto disease is a cause of benign and usually self-limiting lymphadenopathy. Clinicians and pathologists should be aware of this uncommon differential diagnosis since early histologic recognition will minimize potentially and unnecessary evaluations and treatments.

Background: The present study was designed to characterize early structural changes of large arteries in renal transplant recipients with no clinical evidence of cardiovascular disease and normal blood pressure values, and to analyse the relationship between arterial alterations and those of the heart., Methods: Intima media thickness and atherosclerotic plaques of the carotid arteries as well as left ventricular geometry and function were examined in 35 asymtomatic renal transplant recipients and 29 age- and sex-matched healthy controls by high resolution B-mode ultrasound and by echocardiography., Results: Intima-media thickness of the carotid arteries was significantly higher in renal transplant recipients (1.21+/-0.08 mm) than in healthy controls (0.74+/-0.04 mm) (P<0.001). Atherosclerotic plaques were found in the majority of renal transplant recipients (71% vs 14% in healthy controls, P<0.001). Left ventricular mass index was significantly increased in the group of renal transplant recipients (264+/-13 g, 146+/-7 g/m2) when compared with healthy controls (155+/-8 g, 83+/-4 g/m2) (P<0.001). Multiple regression analysis in renal transplant recipients showed that intima media thickness of the carotid arteries was significantly related to left ventricular mass index (P<0.02), but not to age, blood pressure, body mass index, serum creatinine, cholesterol and lipoprotein (a) levels. In the group of healthy controls, intima-media thickness of the carotid artery was related to age (P<0.002), but not to left ventricular mass index or the other independent variables., Conclusions: The present study documents pronounced intima-media thickening in asymptomatic renal transplant recipients. Atherosclerotic lesions are present in most renal transplant recipients with no clinical evidence of cardiovascular disease. We observed a parallelism between arterial wall thickening and left ventricular hypertrophy, although blood pressure levels were normal during haemodialysis therapy and after renal transplantation.

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.

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.

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.

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.

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.

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.

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.

The role of hypertension as a major risk factor for cardio- and cerebrovascular events is well known. Various studies have shown that rigorous antihypertensive treatment can clearly reduce both cerebrovascular and cardiovascular mortality. In recent years, the therapeutic aims of antihypertensive treatment have undergone considerable changes, and to the pre-eminent aim of blood pressure reduction has been added organ protection, which is now a major effect of modern antihypertensive therapy. Today, the selection of an antihypertensive agent is decided not solely on the basis of blood pressure, but to a large extent by the requirements of organ protection and the specifics of the underlying disease. To enable individually effective antihypertensive treatment, a knowledge of the pharmacological profile of the various drugs available, and of the respective broad spectrum of side effects is an important precondition. Although non-drug therapeutic measures also have a part to play in the treatment of hypertension, antihypertensive drugs remain the most important tool for treating essential arterial hypertension.

To investigate the effect of vascular smooth muscle contraction on mechanical vessel wall properties of proximal "elastic" arteries, we investigated the effect of the vasoconstrictor ergotamine on the distensibility of the common carotid artery in 10 migraine patients with ergotamine intake, in 10 control patients with migraine headache but no prior ergotamine intake, and in 10 healthy control subjects. The patients and control subjects were matched for age, blood pressure, and sex. In the ergotamine group, 2.2 +/- 1.4 mg ergotamine tartrate (0.25 to 6 mg) was taken within 12 hours before investigation. Differences in mean 24-hour blood pressure between the study groups were excluded by 24-hour blood pressure recording and differences in arterial wall thickness by high-resolution and differences in arterial wall thickness by high-resolution B-mode ultrasound. A multigate Doppler system was used for measurement of vessel wall movements by M-mode Doppler analysis. Blood pressure was determined by sphygmomanometry. The end-diastolic diameter of the common carotid artery was insignificantly reduced in the ergotamine group compared with the healthy control subjects and control patients (healthy control subjects, 6.6 +/- 0.4 mm; control patients, 6.7 +/- 0.5 mm; patients with ergotamine intake, 6.3 +/- 0.4 mm; P = NS). Arterial distensibility was significantly lower in the patients with ergotamine intake (17.4 +/- 4.0 10(-3)/kPa) than in the healthy control subjects (22.3 +/- 5.1 10(-3)/kPa) and control patients (22.8 +/- 3.6 10(-3)/kPa) (one-way ANOVA, P = .014). The results show that ergotamine reduces the distensibility of the common carotid artery. The data suggest that vascular smooth muscle contraction can modulate the buffering function of the arterial system independently of blood pressure changes.

If arterial hypertension is diagnosed in a patient, it is followed by several consequences. A life-long medical control is necessary. The history, physical examination, and biochemical diagnostics are of great importance. The secondary types of hypertension are specified and the drug therapy is suggested. A special quality in the treatment of arterial hypertension is the treatment during pregnancy.

Objective: To investigate the different effects of hypertension, hyperlipidaemia and atherosclerosis on the visco-elastic properties of large arteries., Design: Vessel wall properties were determined in patients who had been subjected for the first time to coronary arteriography. Normotensive patients with no coronary disease (n = 15), one-vessel disease (n = 15) or two- or three-vessel disease (n = 15), 15 treated hypertensive patients (mean +/- SEM duration of hypertension 9.6 +/- 1.7 years) with no coronary disease and normocholesterolaemia and 15 healthy controls were matched for blood pressure, age and sex., Methods: Arterial distension of the common carotid artery was determined by using a multigate Doppler system. The blood pressure curve was recorded by finger plethysmography., Results: The end-diastolic diameter was significantly higher in the hypertensives (P<0.05) but not significantly different in the normotensives compared with the controls. Arterial distensibility was significantly lower in the hypertensive group [(13.3 +/- 0.8) x 10(-3)/kPa] than in the controls [(19.1 +/- 1.5) x 10(-3)/kP; P<0.01), in the group with no coronary disease [(18.8 +/- 1.3) x 10(-3)/kPa; P<0.01] and in those with one-vessel disease [(17.7 +/- 1.4) x 10(-3)/kPa; P<0.05]. Arterial distensibility was not significantly lower in the hypertensives than in the group with two- or three-vessel disease [(15.0 +/- 1.0) x 10(-3)/kPa; NS). No significant correlation was found between cholesterol or lipoprotein(a) levels and arterial distensibility in the normotensive patients., Conclusions: Hypertension is the predominant factor affecting the visco-elastic properties of large arteries. Arterial compliance is significantly altered only in extensive atherosclerosis.

Since renal allograft rejection is frequently associated with a blunted erythropoiesis, we investigated erythropoietin (EPO) serum concentrations in 17 patients with acute rejection, eight patients with chronic rejection, and 18 transplant recipients with stable graft function. All rejection episodes were proven by biopsy. Erythropoietin serum levels were significantly reduced in patients with chronic rejection (6.2 +/- 3.4 mU/mL; P < 0.01) compared with individuals with acute rejection (35.6 +/- 33.9 mU/mL) or stable graft function (24.0 +/- 19.7 mU/mL). Suppressed EPO levels were associated with marked anemia in chronic rejection patients. In a subgroup of patients with acute rejection and bad responses to an intensified immunosuppressive regimen or with transplant failure, we found significantly suppressed EPO levels (11.6 +/- 6.1 mU/mL) compared with a subgroup of patients with a beneficial acute rejection outcome (57.0 +/- 34.2 mU/mL; P < 0.01). A correlation between histologic parameters of acute rejection and hormone levels showed that signs of moderate glomerulitis were associated with elevated EPO levels, whereas lesions of moderate tubulitis were associated with low values. We conclude that serum EPO may have prognostic value for rejection outcome in renal transplant recipients.

Albumin excretion, Analysis of urinary proteins by polyacrylamide gel electrophoresis (PAGE), and clinical evaluation were performed in 90 HIV-infected patients to assess subclinical renal involvement in HIV infection. Thirteen percent of all patients showed an albumin excretion > 20 mg/liter. Seven of four homosexual patients had albuminuria. Albuminuria occurred exclusively with T4 cell counts below 200/mm3. Polyacrylamide gel electrophoresis indicated glomerular lesions and showed no tubular proteinuria in patients with increased albumin excretion. It is concluded that subclinical renal involvement is not uncommon in HIV infection with T4 cell counts > 200/mm3. HIV-associated nephropathy and heroin-associated nephropathy may not be the main causes of renal involvement. In some cases, opportunistic viral infections may be the cause of microalbuminuria.

Compliance is an important property of the arterial system and abnormalities in compliance can greatly affect cardiovascular function. The elastic properties of the common carotid artery were therefore studied in 24 normotensive hemodialysis patients and 24 healthy normotensives using a noninvasive technique. The hemodialysis patients and the control subjects were matched for blood pressure. Arterial distension was measured by Doppler analysis of the vessel wall movements and blood pressure was recorded by finger-phlethysmography (Finapres). The vessel wall distensibility (DC: 2.49 +/- 0.23 10(-3)/mm Hg; mean +/- SEM) was significantly reduced and the end diastolic diameter (d: 7.3 +/- 0.3 mm) was significantly increased in younger hemodialysis patients (36.3 +/- 2.0 years) when compared with age-related controls (DC: 3.44 +/- 0.24 10(-3)/mm Hg; d: 6.3 +/- 0.3 mm; mean +/- SEM). In older hemodialysis patients (60.2 +/- 2.3 years), there was no significant difference in vessel wall distensibility (DC: 1.55 +/- 0.15 10(-3)/mm Hg) and vessel diameter (d: 7.8 +/- 0.3 mm) as compared with age-matched controls (DC: 1.77 +/- 0.14 10(-3)/mm Hg; d: 7.2 +/- 0.3 mm). The results show that vessel wall distensibility of the common carotid artery is decreased in younger hemodialysis patients as compared with age-matched healthy subjects. The volume expanded state in hemodialysis patients cannot account for the decreased arterial distensibility, since volume depletion by hemodialysis was not associated with a significant change of arterial distensibility (DC 2.14 +/- 0.44 10(-3)/mm Hg before, DC 2.26 +/- 0.45 10(-3)/mm Hg after ultrafiltration, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the contribution of immune mechanisms in the initiation and progression of chronic renal allograft rejection we investigated monocyte-derived cytokine synthesis in vitro in 16 patients with histologically proven chronic rejection; 22 transplant patients with stable function served as controls. Basal tumour necrosis factor-alpha (TNF-alpha) production, measured by L 929 bioassay, was low and not significantly different in both groups. By triggering TNF-alpha formation in vitro by lipopolysaccharide (LPS), high concentrations of TNF-alpha (155.1 +/- 243.0 ng/ml) were measured in monocyte cultures from chronic rejection patients which greatly exceeded the TNF-alpha levels of 11.5 +/- 14.5 ng/ml in the control group. Measurement of interleukin 6 (IL-6) levels by enzyme immunoassay gave similar results, with significantly higher IL-6 concentrations in LPS-triggered monocyte cultures from chronic rejection compared with stable function patients. Additional stimulation of LPS-treated monocytes with interferon-gamma (IFN-gamma) as a priming agent enhanced TNF-alpha formation in stable function patients and, in contrast, slightly reduced monokine formation in chronic rejection patients, which suggests that in this group a high activation level of monocytes has already been reached in vivo by T cell factors such as IFN-gamma. Treatment of monocyte cultures in vitro with prednisolone reduced TNF-alpha formation differently in most but not all cultures from chronic rejection and stable function patients; thus this in vitro test system might be helpful in predicting the benefit of an intensified immunosuppressive regimen for chronic rejection patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Apart from lowering blood pressure, antihypertensive drugs may influence vessel wall function. In a randomized double-blind study, the effect of lisinopril and metoprolol on arterial distensibility was studied in 40 patients with essential hypertension. After a placebo run-in period, the patients were randomly treated with metoprolol (50, 100, or 200 mg) or lisinopril (5, 10, or 20 mg) for 10 weeks. In the lisinopril group, blood pressure decreased after 10 weeks of therapy from 173 +/- 10/102 +/- 5 to 155 +/- 10/85 +/- 3 mm Hg and in the metoprolol group from 167 +/- 12/102 +/- 4 to 153 +/- 8/84 +/- 3 mm Hg. Diameter (millimeters), relative change in diameter (percent), and distensibility (10(-3)/kPa) of the left common carotid artery were determined after the placebo run-in period and after 6 and 10 weeks of antihypertensive therapy. A multigate Doppler system was used to measure the vessel wall movements by Doppler analysis in M-mode; blood pressure was recorded by finger plethysmography (Finapres). Neither lisinopril nor metoprolol influenced the end-diastolic diameter of the common carotid artery after 6 and 10 weeks of treatment. In the lisinopril group, a significant increase of percent change in diameter (P < .05 compared with the baseline value; P < .05 compared with the metoprolol group) and distensibility (P < .01 compared with the baseline value; P < .05 compared with the metoprolol group) was observed. The results show that lisinopril but not metoprolol improves arterial distensibility in essential hypertension. Pressure-independent effects of angiotensin converting enzyme inhibitors may be important modulators of adaptive changes in the arterial wall.

In this study, we compared the cellular functions of cultured glomerular mesangial cells (MC) from spontaneously hypertensive rats (SHR) and from normotensive Wistar-Kyoto rats (WKY) in response to the growth factors insulin-like growth factor I (IGF-I) and platelet-derived growth factor (PDGF). IGF-I and PDGF at a concentration above 2 ng/ml and a combination of both tested growth factors exerted a highly elevated growth response of SHR MC versus WKY MC. The total RNA synthesis induced by IGF-I and PDGF was increased in SHR MC as compared with WKY MC, while the overall protein synthesis showed no differences between both strains. Analysis of cell-associated fibronectin accumulation and incorporation of proline into collagenous proteins revealed an enhanced basal and PDGF-stimulated matrix formation of SHR MC which was not dependent on the increased production of autocrine matrix-stimulatory mediators by SHR MC. Changes of cytosolic free calcium - [Ca2+]i - could not be correlated with the enhanced responsiveness of SHR MC to the tested growth factors. The described differences of cellular functions between SHR and WKY MC may contribute to pronounced glomerular alterations such as glomerulosclerosis seen in primary and secondary forms of hypertension.

Antihypertensive therapy improves the long-term prognosis of patients with mild to moderate essential hypertension and is able to prevent complications. This is also true for the elderly patient with hypertension. A considerable percentage of patients with mild essential hypertension can be adequately treated without drugs. If drug treatment is required, diuretics, beta-blockers, calcium antagonists, and ACE-inhibitors are the agents of first choice. For the individual patient, the appropriate drug should be chosen on the basis of efficacy, lack of side-effects, and depending upon additional diseases, such as cardiac failure, coronary heart disease and renal failure. Only if these selection criteria are fulfilled should differences in prices of the various groups of antihypertensive agents be considered.

The transgenic rat TGR(mRen2)27 is a new monogenetic model in hypertension research that develops fulminant hypertension after the mouse Ren-2d renin gene has been integrated into its genome. To evaluate the molecular mechanism of development of hypertension in this animal model, we measured cytosolic free sodium concentration in intact lymphocytes from seven transgenic rats and eight age-matched normotensive Sprague-Dawley rats using the novel sodium-sensitive fluorescent dye sodium-binding benzofuranisophthalate. Resting cytosolic sodium was significantly higher in transgenic rats compared with Sprague-Dawley rats (31.7 +/- 2.2 versus 18.2 +/- 0.4 mmol/L, mean +/- SEM, P < .001). Inhibition of Na,K-ATPase by 0.5 mmol/L ouabain for 5 minutes significantly increased lymphocytic cytosolic sodium in Sprague-Dawley rats to 36.5 +/- 3.4 mmol/L (P < .001 compared with resting value), whereas no significant change could be observed in transgenic rats (35.4 +/- 0.6 mmol/L), indicating that Na,K-ATPase is less responsive in transgenic rats. The Na,K-ATPase activity from erythrocytes was measured with an enzyme-linked assay. Na,K-ATPase activity was significantly reduced in transgenic rats compared with Sprague-Dawley rats (4.0 +/- 0.3 versus 8.1 +/- 0.6 U/L, P < .001). We concluded that reduced Na,K-ATPase activity leads to elevated cytosolic sodium in this model of genetic hypertension.

Hypertension is a major complication in kidney transplantation and contributes to the high cardiovascular mortality of renal transplanted recipients. The aim of the present study was to evaluate the therapeutic effect of phlebotomy on blood pressure in posttransplant hypertension associated with erythrocytosis. In 12 renal transplanted patients (7 male, 5 female, aged 29-52 years) with erythrocytosis (defined by hematocrit > 52% or hemoglobin > 170 g/l), a 24-hour-monitoring of blood-pressure and heart rate (SpaceLabs SL90207) was performed before, 2 and 6 weeks after phlebotomy. Patients with iron-deficiency and/or transplant rejection were excluded from the study. Ten of 12 patients were on antihypertensive treatment before phlebotomy. Phlebotomy (500 ml) was repeated three times on average within the first two weeks, until hematocrit decreased below 45%. The phlebotomy therapy lowered the hematocrit after two weeks from 54.8 +/- 2.8% to 44.3 +/- 4.2% and 43.0 +/- 5.6% after six weeks. Before phlebotomy, the blood pressure was systolic 153.2 +/- 15.1 mmHg and diastolic 95.2 +/- 9.5 mmHg. After repeated phlebotomy, there was a significant decrease of blood pressure to systolic 139.0 +/- 14.1 and diastolic 85.3 +/- 8.2 mmHg (p < 0.01). Without change of hematocrit and hemoglobin, there was no further change of blood pressure after six weeks (systolic 140.1 +/- 9.9 mmHg, diastolic 86.3 +/- 9.5 mmHg). The heart rate did not change significantly during the therapy. The antihypertensive treatment could be reduced in most of the patients. The present study demonstrates the therapeutic effect of phlebotomy in posttransplant hypertension associated with erythrocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

This is a case report of heparin-associated thrombocytopenia syndrome (white clot syndrome). An 81-Year-old patient was treated with sodium-heparin for proximal deep-venous thrombosis and pulmonary embolism. During administration of heparin, the platelet count decreased to a nadir of 27/nl on day 14 after initiation of this therapy. We also observed a recurrence of pulmonary embolism as well as arterial thromboembolism in the right arm and the right leg. After immediate discontinuation of heparin therapy and change of anticoagulation to oral anticoagulants with overlapping administration of a low molecular weight heparin and application of immunoglobulins, we observed total recanalization of the arterial occlusions, normalization of lung-perfusion scan and rapid recovery of the platelet count.

Circadian rhythm of blood pressure and of heart rate was studied in patients with hyperthyroidism (n = 10), pheochromocytoma (n = 8), primary hyperaldosteronism (n = 7), and in a control group of essential hypertensive patients (n = 18) and of normotensive healthy subjects (n = 11). 24-hour blood pressure was monitored non-invasively using SpaceLabs (SL 90207) with 8-min intervals in the daytime (8 a.m. to 10 p.m.) and 30-min intervals during night-time (10 p.m. to 8 a.m.). To characterize circadian blood pressure rhythm the difference between the mean blood pressure during daytime and that during night-time was calculated. In patients with hyperthyroidism the day-night difference of the systolic and diastolic blood pressure and of the heart rate was significantly reduced when compared to the normotensive control group (p < 0.05). The day-night difference of the systolic and diastolic blood pressure was significantly lower in the group with pheochromocytoma and hyperthyroidism than in the essential hypertensive controls (p < 0.05); the day-night difference of the heart rate was similar. In the patients with primary hyperaldosteronism the day-night differences of the systolic and diastolic blood pressure and of the heart rate was similar to those in essential hypertensive controls. We conclude that endocrine disorders affecting sympathetic activity like pheochromocytoma or hyperthyroidism influence the circadian blood pressure rhythm, whereas the renin-aldosterone-system has no major impact on the diurnal blood pressure variation. The results therefore support the hypothesis that circadian blood pressure variation is mainly mediated by a modulation of the sympathetic tone.

To assess the influence of long-term hemodialysis on arterial compliance, the elastic vessel wall properties of the common carotid artery were determined in 20 normotensive renal transplant recipients (age 44.7 +/- 4.1 years) 8-12 weeks after first transplantation and in 10 healthy controls (age 45.9 +/- 5.2 years). Arterial distension was measured by using a multigate pulsed Doppler system, blood pressure curve was recorded by finger-plethysmography. 10 patients with a prior long-term hemodialysis of 51 +/- 11 months were compared to 10 patients with a prior short hemodialysis of 18 +/- 7 months. The patients and controls had been matched in respect of age, sex and blood pressure. In the long and short-term hemodialysis group, the proportion of patients (n = 10) with a history of mild hypertension was similar--mild hypertension for 25 +/- 10 months (n = 5) and for 27 +/- 9 months (n = 5). In the group with long-term hemodialysis, the cross-sectional compliance and the distensibility coefficient was significantly reduced in comparison to the group with short-term hemodialysis (p < 0.005) and to the control group (p < 0.001). A significant inverse correlation between the hemodialysis period and the distensibility coefficient (r = -0.59; p < 0.005) showed a decrease in arterial compliance with the length of hemodialysis treatment. The results demonstrate that vessel wall elasticity decreases with the length of hemodialysis treatment and is reduced by hemodialysis-dependent factors, which are detached from sustained arterial hypertension. As cause of reduced arterial compliance in long-term hemodialysis hypervolemia, hypercirculation and disturbed calcium-phosphate metabolism is suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

A 17-year old girl presented with recurrent seizures, strokes, fatigue, vomiting, cerebellar ataxia, dementia and hypertrichosis. Further examinations showed jerking left-sided arm reflexes, partial internal deafness and myopathy. CT and MR of the skull revealed radiolucencies within the cerebral matter of the cortex and the medulla. Laboratory tests showed increased levels of lactate and pyruvate in serum and cerebro-spinal fluid. Microscopic examination of muscular tissue showed "ragged red fibers". Electron microscopy yielded crystal inclusions in mitochondria. The symptoms represented the complete picture of the so-called MELAS/MERRF-complex, which can be easily misdiagnosed as strokes and seizures of unknown cause.