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Biomedical subjects

E Mervaala

Publications and source records attributed to E Mervaala.

At least 19 recordsLinked to original sources
PubMed2005

Why and how to implement sodium, potassium, calcium, and magnesium changes in food items and diets?

The present average sodium intakes, approximately 3000-4500 mg/day in various industrialised populations, are very high, that is, 2-3-fold in comparison with the current Dietary Reference Intake (DRI) of 1500 mg. The sodium intakes markedly exceed even the level of 2500 mg, which has been recently given as the maximum level of daily intake that is likely to pose no risk of adverse effects on blood pressure or otherwise. By contrast, the present average potassium, calcium, and magnesium intakes are remarkably lower than the recommended intake levels (DRI). In USA, for example, the average intake of these mineral nutrients is only 35-50% of the recommended intakes. There is convincing evidence, which indicates that this imbalance, that is, the high intake of sodium on one hand and the low intakes of potassium, calcium, and magnesium on the other hand, produce and maintain elevated blood pressure in a big proportion of the population. Decreased intakes of sodium alone, and increased intakes of potassium, calcium, and magnesium each alone decrease elevated blood pressure. A combination of all these factors, that is, decrease of sodium, and increase of potassium, calcium, and magnesium intakes, which are characteristic of the so-called Dietary Approaches to Stop Hypertension diets, has an excellent blood pressure lowering effect. For the prevention and basic treatment of elevated blood pressure, various methods to decrease the intake of sodium and to increase the intakes of potassium, calcium, and magnesium should be comprehensively applied in the communities. The so-called 'functional food/nutraceutical/food-ceutical' approach, which corrects the mineral nutrient composition of extensively used processed foods, is likely to be particularly effective in producing immediate beneficial effects. The European Union and various governments should promote the availability and use of such healthier food compositions by tax reductions and other policies, which make the healthier choices cheaper than the conventional ones. They should also introduce and promote the use of tempting nutrition and health claims on the packages of healthier food choices, which have an increased content of potassium, calcium, and/or magnesium and a lowered content of sodium. Such pricing and claim methods would help the consumers to choose healthier food alternatives, and make composition improvements tempting also for the food industry.

Adult↗
PubMed2004

Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes.

AIMS/HYPOTHESIS: Diabetes is known to reduce survival after myocardial infarction. Our aim was to examine whether diabetes is associated with enhanced cardiomyocyte apoptosis and thus interferes with the post-infarction remodelling process in myocardium in rat. METHODS: Four weeks after intravenous streptozotocin (diabetic groups) or citrate buffer (controls) injection, myocardial infarction was produced by ligation of left descending coronary artery. Level of cardiomyocyte apoptosis was quantified by TUNEL and caspase-3 methods. Collagen volume fraction and connective tissue growth factor were determined under microscope. Left ventricular dimensions were evaluated by echocardiography and planimetry. RESULTS: The number of apoptotic cardiomyocytes was equally high in diabetic and non-diabetic rats after 1 week from infarction. At 12 weeks after infarction the number of apoptotic cells was higher in the diabetic as compared to non-diabetic rats both in the border zone of infarction and in non-infarcted area. Correspondingly, left ventricular end diastolic diameter, relative cardiac weight, connective tissue growth factor-expression and fibrosis were increased in diabetic compared with non-diabetic rats with myocardial infarction. CONCLUSION/INTERPRETATION: Sustained cardiomyocyte apoptosis, left ventricular enlargement, increased cardiac fibrosis and enhanced profibrogenic connective tissue growth factor expression were detected after myocardial infarction in experimental diabetes. Apoptotic myocyte loss could be an important mechanism contributing to progressive dilatation of the heart and poor prognosis after myocardial infarction in diabetes.

Animals↗
PubMed2004

Preoperative clinical evaluation, outline of surgical technique and outcome in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common type of refractory epilepsy. The mechanisms of epileptogenesis and seizure semiology of the mesial and neocortical temporal lobe epilepsy are discussed. The evaluation and selection of patients for TLE surgery requires team work: the different clinical aspects of neuropsychological evaluation, magnetic resonance and functional imaging (positron emission tomography, single photon emission computed tomography and magnetoenephalography) are reviewed. In our programme of epilepsy surgery at Kuopio University Hospital, Finland, we have performed 230 temporal resections from 1988 until 2002. Preoperative diagnostic EEG-videotelemetry often required intracranial monitoring and it has proved to be safe and efficient. The indications and technique for tailored temporal lobe resection with amygdalohippocampectomy used in our institution, as well as the complications, are described. Our analysis of outcome after temporal lobe surgery included 140 consecutive adult patients between 1988 and 1999; one year after the operation in unilateral TLE the Engel I-II outcome was observed in 68% of the patients. Outcome of surgery improved significantly after introduction of the standardised MR imaging protocol from 1993; 74% of patients with unilateral TLE achieved Engel I-II outcome.

Electroencephalography↗
PubMed2002

High-dose thiopental in the treatment of refractory status epilepticus in intensive care unit.

The authors studied prospectively the effects of thiopental anesthesia on seizure control, hemodynamics, and the course of intensive care in 10 patients with refractory status epilepticus. Clinical and electrophysiological seizures were terminated in every patient. Hemodynamically, thiopental was well tolerated, but slow recovery from anesthesia prolonged the need for intensive care.

Adolescent↗
PubMed2002

Long term outcome of temporal lobe epilepsy surgery: analyses of 140 consecutive patients.

OBJECTIVE: To analyse the long term results of temporal lobe epilepsy surgery in a national epilepsy surgery centre for adults, and to evaluate preoperative factors predicting a good postoperative outcome on long term follow up. METHODS: Longitudinal follow up of 140 consecutive adult patients operated on for drug resistant temporal lobe epilepsy. RESULTS: 46% of patients with unilateral temporal lobe epilepsy became seizure-free, 10% had only postoperative auras, and 15% had rare seizures on follow up for (mean (SD)) 5.4 (2.6) years, range 0.25 to 10.5 years. The best outcome was after introduction of a standardised magnetic resonance (MR) imaging protocol (1993-99): in unilateral temporal lobe epilepsy, 52% of patients became seizure-free, 7% had only postoperative auras, and 17% had rare seizures (median follow up 3.8 years, range 0.25 to 6.5 years); in palliative cases (incomplete removal of focus), a reduction in seizures of at least 80% was achieved in 71% of cases (median follow up 3.1 years, range 1.1 to 6.8 years). Most seizure relapses (86%) occurred within one year of the operation, and outcome at one year did not differ from the long term outcome. Unilateral hippocampal atrophy with or without temporal cortical atrophy on qualitative MR imaging (p < 0.001, odds ratio (OR) 5.2, 95% confidence interval (CI) 2.0 to 13.7), other unitemporal structural lesions on qualitative MR imaging (p < or = 0.001, OR 6.9, 95% CI 2.2 to 21.5), onset of epilepsy before the age of five years (p < 0.05, OR 2.9, 95% CI 1.2 to 7.2), and focal seizures with ictal impairment of consciousness and focal ictal EEG as a predominant seizure type (p < 0.05, OR 3.4, 95% CI 1.2 to 9.1) predicted Engel I-II outcome. Hippocampal volume reduction of at least 1 SD from the mean of controls on the side of the seizure onset (p < 0.05, OR 3.1, 95% CI 1.1 to 9.2) also predicted Engel I-II outcome. CONCLUSIONS: Outcome at one year postoperatively is highly predictive of long term outcome after temporal lobe epilepsy surgery. Unitemporal MR imaging abnormalities, early onset of epilepsy, and seizure type predominance are factors associated with good postoperative outcome.

Adult↗
PubMed2001

Amelioration of angiotensin II-induced cardiac injury by a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have effects that extend beyond cholesterol reduction. We used an angiotensin (Ang) II-dependent model to test the hypothesis that cerivastatin ameliorates cardiac injury. METHODS AND RESULTS: We treated rats transgenic for human renin and angiotensinogen (dTGR) chronically from weeks 4 to 7 with cerivastatin (0.5 mg/kg by gavage). We used immunohistochemistry, electrophoretic mobility shift assays, and reverse transcription-polymerase chain reaction techniques. Compared with control dTGR, dTGR treated with cerivastatin had reduced mortality, blood pressure, cardiac hypertrophy, macrophage infiltration, and collagen I, laminin, and fibronectin deposition. Basic fibroblast growth factor mRNA and protein expression were markedly reduced, as was interleukin-6 expression. The transcription factors NF-kappaB and AP-1 were substantially less activated, although plasma cholesterol was not decreased. CONCLUSIONS: These results suggest that statins ameliorate Ang II-induced hypertension, cardiac hypertrophy, fibrosis, and remodeling independently of cholesterol reduction. Although the clinical significance remains uncertain, the results suggest that statins interfere with Ang II-induced signaling and transcription factor activation, thereby ameliorating end-organ damage.

Angiotensin II↗
PubMed2001

Cyclosporine induces myocardial connective tissue growth factor in spontaneously hypertensive rats on high-sodium diet.

BACKGROUND: The introduction of cyclosporine (CsA) has led to an improvement in the prognosis of solid organ transplantation. However, drug-induced hypertension and nephrotoxicity, associated with the development of atherosclerosis and coronary heart disease, still worsen the long-term outcome of CsA-treated patients. Whether the CsA-induced myocardial changes are associated with the induction of connective tissue growth factor (CTGF), a recently found polypeptide implicated in extracellular matrix synthesis, is not known. METHODS: Spontaneously hypertensive rats (8-9 weeks old) were treated with CsA (5 mg x kg(-1) x d(-1) subcutaneously) for 6 weeks. The influence of angiotensin-converting enzyme inhibition (enalapril 30 mg x kg(-1) x d(-1) orally) and angiotensin-1 receptor blockade (valsartan 3 and 30 mg x kg(-1) x d(-1) orally) on CsA toxicity was also investigated. Myocardial morphology was examined, and vascular lesions were scored. Localization and the quantitative expression of CTGF, as well as collagen I and collagen III, mRNA were evaluated by in situ hybridization and Northern blot. RESULTS: CsA-induced hypertension and nephrotoxicity were associated with myocardial infarcts and vasculopathy of the coronary arteries. CsA increased myocardial CTGF, collagen I, and collagen III mRNA expressions by 91%, 198%, and 151%, respectively. CTGF mRNA expression colocalized with the myocardial lesions. Blockade of the renin-angiotensin system prevented vascular damage and the CsA-induced CTGF, collagen I, and collagen III mRNA overexpressions in the heart. CONCLUSIONS: CsA increases CTGF, collagen I, and collagen III mRNA expressions in the heart. The induction of CTGF gene is mediated, at least in part, by angiotensin II.

Animals↗
PubMed2001

[18F]FDG-PET reveals temporal hypometabolism in patients with temporal lobe epilepsy even when quantitative MRI and histopathological analysis show only mild hippocampal damage.

BACKGROUND: The relationship between reduced glucose metabolism in positron emission tomography with fludeoxyglucose F 18 ([(18)F]FDG-PET) and hippocampal damage (HD) in patients with temporal lobe epilepsy is still unclear. OBJECTIVE: To determine whether the presence and severity of HD verified by quantitative magnetic resonance imaging (QMRI) and histopathological analysis affect the degree of hypometabolism. PATIENTS AND METHODS: Sixteen patients with drug-resistant temporal lobe epilepsy underwent [(18)F]FDG-PET and QMRI (hippocampal volumetry and T2 relaxometry) before surgery. Histopathological analysis of the hippocampus included measurements of neuronal loss, proliferation of glial cells, and mossy fiber sprouting. The asymmetry in glucose metabolism described the degree of hypometabolism. RESULTS: Temporal hypometabolism was not related to severity of HD as measured by QMRI or histopathological analysis. The degree of hypometabolism did not differ in patients with mild, moderate, or severe HD. In addition, [(18)F]FDG-PET revealed significant temporal hypometabolism even though hippocampal QMRI findings were normal or showed only mild HD. Thus, glucose consumption was reduced over and above the histopathological changes. CONCLUSIONS: [(18)F]FDG-PET is sensitive for localizing the epileptogenic region in patients with temporal lobe epilepsy. However, it is insensitive to reflect the severity of HD.

Adolescent↗
PubMed2001

SPECT and neuropsychological performance in severe depression treated with ECT.

BACKGROUND: In severe depression, studies of regional cerebral blood flow (rCBF) by SPECT have not produced uniform results. The association between changes in SPECT and electroconvulsive therapy (ECT) has shown somewhat conflicting data. No data are available on benzodiazepine receptor function SPECT studies in ECT. METHODS: Twenty drug-resistant adult inpatients fulfilling the DSM-IIIR criteria for major depression were studied by SPECT (rCBF by relative ECD uptake in all, and benzodiazepine receptor function by iomazenil uptake in five subjects) before and 1 week after clinically successful bitemporal ECT. Clinical and neuropsychological test scores were used as references for the possible changes in SPECT. RESULTS: An increased perfusion after ECT was observed in right temporal and bilateral parietal cortices, whereas no reductions in relative ECD uptake were seen after ECT. Iomazenil-SPECT revealed a highly significant increase in the benzodiazepine receptor uptake in all studied cortical regions except temporal cortices. CONCLUSIONS: Clinically successful ECT was associated with changes in vascular perfusion and GABAergic neurotransmission, providing new evidence for the mechanism of action of ECT and for the neurobiology of severe drug-resistant depression.

Adult↗
PubMed2001

MR volumetry of the entorhinal, perirhinal, and temporopolar cortices in drug-refractory temporal lobe epilepsy.

BACKGROUND AND PURPOSE: The occurrence of damage in the entorhinal, perirhinal, and temporopolar cortices in unilateral drug-refractory temporal lobe epilepsy (TLE) was investigated with quantitative MR imaging. METHODS: Volumes of the entorhinal, perirhinal, and temporopolar cortices were measured in 27 patients with unilateral drug-refractory TLE, 10 patients with extratemporal partial epilepsy, and 20 healthy control subjects. All patients with TLE were evaluated for epilepsy surgery and underwent operations. RESULTS: In left TLE, the mean volume of the ipsilateral entorhinal cortex was reduced by 17% (P <.001 compared with control subjects) and that of the ipsilateral temporopolar cortex by 17% (P <.05). In right TLE, the mean ipsilateral entorhinal volume was reduced by 13% (P < or =.01), but only in patients with hippocampal atrophy. Asymmetry ratios also indicated ipsilateral cortical atrophy. When each patient was analyzed individually, the volume of the ipsilateral hippocampus was reduced (> or = 2 SD from the mean of controls) in 63% and that of the entorhinal cortex in 52% of patients with TLE. Furthermore, ipsilateral entorhinal (left: r = 0.625, P <.001; right: r = 0.524, P < or =.01), perirhinal (left: r = 0.471, P <.05), and temporopolar (right: r = 0.556, P <.01) volumes correlated with ipsilateral hippocampal volumes. There was no association, however, with clinically or pathologically identified causes of epilepsy, duration of epilepsy, or age at onset of epilepsy. Mean cortical volumes were unaffected in extratemporal partial epilepsy. CONCLUSION: Subpopulations of patients with unilateral TLE have ipsilateral damage in the entorhinal and temporopolar cortices. The damage is associated with hippocampal damage.

Adolescent↗
PubMed2001

Diet enrichment with calcium and magnesium enhances the cholesterol-lowering effect of plant sterols in obese Zucker rats.

BACKGROUND AND AIM: Recent clinical studies have demonstrated that plant sterols moderately lower serum cholesterol levels in patients with mild hypercholesterolemia. Furthermore, there is evidence suggesting that mineral nutrients, such as calcium and magnesium, may also decrease serum cholesterol concentrations. In this study, we tested the hypothesis that supplementation with mineral nutrients may enhance the cholesterol-lowering effect of plant sterols in obese Zucker rats. Furthermore, we compared the lipid-lowering effects of monovalent sodium and potassium cations with those of divalent calcium and magnesium cations. METHODS AND RESULTS: A Western-type high-fat/high-cholesterol diet increased serum cholesterol by 175% and liver cholesterol by 65% in comparison with a low-fat/low-cholesterol control diet. On the contrary, the high-fat/high-cholesterol diet decreased intestinal cholesterol absorption, as assessed by means of serum campesterol-, sitosterol-, and sitostanol-to-cholesterol ratios, thus indicating that it was under negative feedback regulation. Supplementation of the high-fat/high-cholesterol diet with plant sterols or mineral nutrients partially prevented the diet-induced increased in serum cholesterol and, when given concurrently, their cholesterol-lowering effect was enhanced. Their combination also effectively prevented the diet-induced increase in liver cholesterol concentration, and had beneficial effects on liver and myocardial hypertrophy, and the development of obesity. These beneficial effects were at least partially mediated by an enhanced blockade of intestinal cholesterol absorption. Interestingly, only divalent cations enhanced the cholesterol-lowering effect of plant sterols, thus supporting the idea that the lipid-lowering effect of divalent cations is related to the formation of insoluble and inabsorbable calcium and magnesium chelates with fatty acids. CONCLUSIONS: Our findings indicate that the cholesterol-lowering effect of plant sterols is enhanced by the co-administration of divalent calcium and magnesium cations but not by monovalent sodium and potassium cations.

Analysis of Variance↗
PubMed2000

Down-regulation of renal glutathione synthesis by systemic nitric oxide synthesis inhibition in spontaneously hypertensive rats.

Nitric oxide stimulates in vitro the synthesis of glutathione, an abundant thiol with a number of functions such as detoxification of xenobiotics and reactive oxygen species. In order to study this relationship in an animal model of hypertension, we treated spontaneously hypertensive rats (SHR) either with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) or with a nitric oxide donor isosorbide-5-mononitrate (IS-5-MN). Inhibition of nitric oxide synthesis led to malignant hypertension and to a marked decrease in glutathione synthesis through down-regulation of the rate-limiting enzyme gamma-glutamylcysteine synthetase (GCS). The reduction in GCS activity was further augmented in SHR on a high sodium diet. Renal GCS activity in untreated SHR was 234 +/- 14 and 240 +/- 18 nmol/min/mg protein (mean +/- SD) on a low and high sodium diet, respectively. When L-NAME was included in the diet, the activities dropped to 173 +/- 28 and 123 +/- 28 for the low and high sodium diets, respectively. IS-5-MN attenuated the rise in blood pressure induced by sodium chloride, but did not affect the GCS activity. The mechanism of GCS stimulation by nitric oxide is not known, but our results combined with the literature suggest that a relatively high concentration of nitric oxide is needed.

Animals↗
PubMed2000

Magnesium. An update on physiological, clinical and analytical aspects.

There is an increased interest in the role of magnesium ions in clinical medicine, nutrition and physiology. The characteristics of the binding of magnesium and calcium ions to various components, macromolecules and biological membranes are described. Magnesium affects many cellular functions, including transport of potassium and calcium ions, and modulates signal transduction, energy metabolism and cell proliferation. The mechanism of cellular uptake and efflux of magnesium, its intracellular transport, intestinal absorption, renal excretion and the effect of hormones on these are reviewed. Magnesium deficiency is not uncommon among the general population: its intake has decreased over the years especially in the western world. The magnesium supplementation or intravenous infusion may be beneficial in various diseased states. Of special interest is the magnesium status in alcoholism, eclampsia, hypertension, atherosclerosis, cardiac diseases, diabetes, and asthma. The development of instrumentation for the assay of ionized magnesium is reviewed, as are the analytical procedures for total magnesium in blood and free magnesium in the cytosol. The improved procedures for the assay of different magnesium states are useful in understanding the role of magnesium in health and disease.

Calcium↗
PubMed2000

MRI volumetry of the hippocampus, amygdala, entorhinal cortex, and perirhinal cortex after status epilepticus.

Neuronal damage has been observed in the medial temporal lobe of both humans and animals following status epilepticus. The aim of the present study was to investigate the occurrence of medial temporal lobe damage in status epilepticus patients treated in hospital with a predetermined protocol and to assess whether the changes progress in a long-term follow-up. The volumes of the hippocampus, amygdala, entorhinal and perirhinal cortices were measured using magnetic resonance imaging (MRI) in nine adult patients with status epilepticus 3 weeks, 6 and 12 months after the insult. The control group included 20 healthy subjects. The etiology of status epilepticus was an acute process in one patient and a chronic process in eight cases. The mean duration of secondarily generalized tonic-clonic status epilepticus episodes was 1 h and 44 min. Volumetric MRI indicated that none of the patients developed marked volume reduction in the hippocampus, amygdala, or the entorhinal and perirhinal cortices during the 1-year follow-up period. Status epilepticus does not invariably lead to a progressive volume reduction in the medial temporal lobe structures of adult patients treated promptly in hospital with a predetermined protocol for rapid cessation of seizure activity.

Adolescent↗
PubMed2000

Quantitative MRI of the hippocampus and amygdala in severe depression.

BACKGROUND: There is little evidence to support possible structural changes in the amygdala and hippocampus of patients with severe depression. METHODS: Quantitative MRI of the amygdala and hippocampus, as well as proton spectroscopy (MRS) of mesial temporal structures were studied in 34 drug-resistant in-patients with major depression and compared with 17 age-matched controls. Volumetric MRI data were normalized for brain size. RESULTS: The volume of the left hippocampus was significantly smaller in the patients compared with the controls. Both groups exhibited similar significant hippocampal asymmetry (left smaller than right). The patients, but not the controls, had significant asymmetry of the amygdalar volumes (right smaller than left). No differences were observed between the patients and controls in the T2 relaxation times for the hippocampus and amygdala. Mesial temporal lobe MRS revealed a significantly elevated choline/creatine ratio in the patients compared with the controls. CONCLUSIONS: This quantitative MRI study provides support for a possible association between structural and biochemical substrates and severe drug-resistant major depression.

Adult↗
PubMed2000

Development of chronic allograft rejection and arterial hypertension in Brown Norway rats after renal transplantation.

The cardiovascular and renal pathophysiology associated with chronic renal allograft rejection under triple drug immunosuppressive treatment was studied using a recently developed model (Brown Norway (BN) rats) in a 6-week experiment. Renal transplantation was performed to 10-week-old rats in a rat strain combination of Dark Agouti (DA) --> BN. The right kidney was removed from another group of BN rats (uninephrectomized). A triple drug treatment comprising cyclosporine (10 mg/kg subcutaneously, s.c.), azathioprine (2 mg/kg s.c.) and methylprednisolone (1.6 mg/kg s.c.) was given to each rat daily for 6 weeks. A control group underwent no operations nor drug treatment. After the transplantation, the systolic blood pressure in this group was increased from 116 +/- 2 to 166 +/- 2 mmHg, while in the uninephrectomized group the rise was from 115 +/- 4 to 146 +/- 4 mmHg, and no change was observed in the blood pressures of the control group. The vascular relaxation responses of mesenteric arterial rings in vitro to acetylcholine were inhibited in both the transplantation group and the uninephrectomized group as compared with the control group, but few significant differences were found in the contraction responses to noradrenaline and potassium chloride. Graft histology was examined after 6 weeks, quantified by using the chronic allograft damage index (CADI). Changes specific to a chronic rejection reaction were observed in the allografts (CADI mean 6.0) but no injuries were seen in the rats' own kidneys (CADI mean 1.2). Our findings show that allograft rejection in BN rats after renal transplantation is associated with the development of arterial hypertension. The combination of cyclosporine, methylprednisolone and azathioprine also rises blood pressure in uninephrectomized BN rats. The hypertensive effects of the drug treatment and graft rejection are associated with endothelial dysfunction.

Animals↗
PubMed2000

Cyclosporin A protects against angiotensin II-induced end-organ damage in double transgenic rats harboring human renin and angiotensinogen genes.

Leukocyte infiltration and adhesion molecule activation play a central role in the pathogenesis of angiotensin II (Ang II)-induced end-organ damage in double transgenic rats (dTGR) harboring human renin and angiotensinogen genes. We tested the hypothesis that the immunosuppressive agent cyclosporine (CsA) protects against the Ang II-induced myocardial and renal damage in dTGR. Furthermore, we investigated the influence of CsA on interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) expression and the DNA binding activity of transcription factor necrosis factor-kappaB (NF-kappaB). The 4-week-old rats were divided into 4 groups: (1) control dTGR (n=20), (2) dTGR plus CsA (5 mg/kg SC for 3 weeks, n=15), (3) normotensive Sprague-Dawley (SD) rats (n=10), and (4) SD rats plus CsA (n=8). In dTGR, CsA completely prevented cardiovascular death (0 of 15 versus 9 of 20), decreased 24-hour albuminuria by 90% and systolic blood pressure by 35 mm Hg, and protected against the development of cardiac hypertrophy. Whole blood CsA concentrations 24 hours after the last drug treatment were 850+/-15 ng/mL. Semiquantitative ED-1 and Ki-67 (a nuclear cell proliferation-associated antigen) scoring showed that CsA prevented perivascular monocyte/macrophage infiltration and prevented cell proliferation in the kidneys and hearts of dTGR, respectively. The beneficial effects of CsA were, at least in part, mediated by the suppression of IL-6 and iNOS expression. Electrophoretic mobility shift assay revealed that CsA regulated inflammatory response in part through the NF-kappaB transcriptional pathway. In contrast to dTGR, CsA increased blood pressure in normotensive SD rats by 10 mm Hg and had no effect on cardiac mass or 24-hour urinary albumin excretion. Perivascular monocyte/macrophage infiltration, IL-6, and iNOS expression or cell proliferation were not affected by CsA in SD rats. Our findings indicate that CsA protects against Ang II-induced end-organ damage and underscore the central role of vascular inflammatory response in the pathogenesis of myocardial and renal damage in dTGR. The beneficial effects of CsA in the kidney and heart are mediated, at least in part, by suppression of IL-6 and iNOS expression via NF-kappaB transcriptional pathway.

Albuminuria↗