Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

<p>Abstract</p> <p>Background</p> <p>Endothelin-1 and angiotensin II are strong vasoconstrictors. Patients with ischemic heart disease have elevated plasma levels of endothelin-1 and angiotensin II and show increased vascular tone. The aim of the present study was to examine the endothelin and angiotensin II receptor expression in subcutaneous arteries from patients with different degrees of ischemic heart disease.</p> <p>Methods</p> <p>Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A (ET_A) and type B (ET_B), and angiotensin type 1 (AT₁) and type 2 (AT₂) receptors expression and function were examined using immunohistochemistry, Western blot and <it>in vitro </it>pharmacology.</p> <p>Results</p> <p>ET_Aand, to a lesser extent, ET_Breceptor staining was observed in the healthy vascular smooth muscle cells. The level of ET_Breceptor expression was higher in patients undergoing CABG surgery (250% ± 23%; P < 0.05) and in the patients with angina pectoris (199% ± 6%; P < 0.05), than in the healthy controls (100% ± 28%). The data was confirmed by Western blotting. Arteries from CABG patients showed increased vasoconstriction upon administration of the selective ET_Breceptor agonist sarafotoxin S6c, compared to healthy controls (P < 0.05). No such difference was found for the ET_Areceptors. AT₁and, to a lesser extent, AT₂receptor immunostaining was seen in the vascular smooth muscle cells. The level of AT₁receptor expression was higher in both the angina pectoris (128% ± 25%; P < 0.05) and in the CABG patients (203% ± 41%; P < 0.05), as compared to the healthy controls (100% ± 25%). The increased AT₁receptor expression was confirmed by Western blotting. Myograph experiment did however not show any change in vasoconstriction to angiotensin II in CABG patients compared to healthy controls (P = n.s).</p> <p>Conclusion</p> <p>The results demonstrate, for the first time, upregulation of ET_Band AT₁receptors in vascular smooth muscle cells in ischemic heart disease. These receptors may play a role in the pathophysiology of ischemic heart disease and could provide important targets for pharmaceutical interventions.</p

Prevalence of adult ADHD in an all-female prison unit.

There is increasing evidence suggesting a link between ADHD and criminality, including a strong association between ADHD symptoms and the likelihood of being on probation or in prison. Most studies investigating the prevalence of ADHD in prison populations have focused on adult male offenders. In the current study, 69 female prisoners were screened for both childhood and adult ADHD symptoms using the Barkley Adult ADHD Rating Scale-IV. The results indicate that 41 % of the prisoners met the diagnostic criteria for ADHD in childhood and continued to meet criteria for ADHD as adults. More importantly, young female prisoners (aged 18-25) were significantly more likely to report symptoms of ADHD than older prisoners. Prisoners who reported symptoms of ADHD also reported high levels of impairment associated with these symptoms. A better understanding of the prevalence of ADHD in female prison units can highlight specific areas for intervention during rehabilitation, as well as the management of serious incidents within prison

Inhibition of PKC activity blocks the increase of ET(B )receptor expression in cerebral arteries

BACKGROUND: Previous studies have shown that there is a time-dependent upregulation of contractile endothelin B (ET(B)) receptors in middle cerebral arteries (MCA) after organ culture. This upregulation is dependent on mitogen-activated protein kinases and possibly protein kinase C (PKC). The aim of this study was to examine the effect of PKC inhibitors with different profiles on the upregulation of contractile ET(B )receptors in rat MCA. Artery segments were incubated for 24 hours at 37°C. To investigate involvement of PKC, inhibitors were added to the medium before incubation. The contractile endothelin-mediated responses were measured and real-time PCR was used to detect endothelin receptor mRNA levels. Furthermore, immunohistochemistry was used to demonstrate the ET(B )receptor protein distribution in the MCA and Western blot to measure which of the PKC subtypes that were affected by the inhibitors. RESULTS: The PKC inhibitors bisindolylmaleimide I, Ro-32-0432 and PKC inhibitor 20–28 attenuated the ET(B )receptor mediated contractions. Furthermore, Ro-32-0432 and bisindolylmaleimide I decreased ET(B )receptor mRNA levels while PKC inhibitor 20–28 reduced the amount of receptor protein on smooth muscle cells. PKC inhibitor 20–28 also decreased the protein levels of the five PKC subtypes studied (α, βI, γ, δ and ε). CONCLUSION: The results show that PKC inhibitors are able to decrease the ET(B )receptor contraction and expression in MCA smooth muscle cells following organ culture. The PKC inhibitor 20–28 affects the protein levels, while Ro-32-0432 and bisindolylmaleimide I affect the mRNA levels, suggesting differences in activity profile. Since ET(B )receptor upregulation is seen in cerebral ischemia, the results of the present study provide a way to interfere with the vascular involvement in cerebral ischemia

Protein kinase C inhibition attenuates vascular ET(B )receptor upregulation and decreases brain damage after cerebral ischemia in rat

BACKGROUND: Protein kinase C (PKC) is known to be involved in the pathophysiology of experimental cerebral ischemia. We have previously shown that after transient middle cerebral artery occlusion, there is an upregulation of endothelin receptors in the ipsilateral middle cerebral artery. The present study aimed to examine the effect of the PKC inhibitor Ro-32-0432 on endothelin receptor upregulation, infarct volume and neurology outcome after middle cerebral artery occlusion in rat. RESULTS: At 24 hours after transient middle cerebral artery occlusion (MCAO), the contractile endothelin B receptor mediated response and the endothelin B receptor protein expression were upregulated in the ipsilateral but not the contralateral middle cerebral artery. In Ro-32-0432 treated rats, the upregulated endothelin receptor response was attenuated. Furthermore, Ro-32-0432 treatment decreased the ischemic brain damage significantly and improved neurological scores. Immunohistochemistry showed fainter staining of endothelin B receptor protein in the smooth muscle cells of the ipsilateral middle cerebral artery of Ro-32-0432 treated rats compared to control. CONCLUSION: The results suggest that treatment with Ro-32-0432 in ischemic stroke decreases the ischemic infarction area, neurological symptoms and associated endothelin B receptor upregulation. This provides a new perspective on possible mechanisms of actions of PKC inhibition in cerebral ischemia

Chlamydophila pneumoniae in Cardiovascular Diseases : Clinical and Experimental Studies

Chlamydophila pneumoniae (C. pneumoniae) has been suggested as a stimulator of chronic inflammation in atherosclerosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 50% of patients with stable angina pectoris or acute coronary syndrome undergoing coronary artery bypass grafting. C. pneumoniae mRNA, a marker of replicating bacteria, was demonstrated in 18% of the aortic biopsies. Inflammation may have a role in the pathogenesis of thoracic aortic aneurysm, aortic dissection and aortic valve stenosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 26% of thoracic aortic aneurysm patients and in 11% of aortic dissection patients undergoing thoracic surgery and in 22% of stenotic aortic heart valves from patients undergoing aortic valve replacement. No bacterial mRNA was demonstrated in these aortic biopsies, nor in the valves, suggesting that the infection has passed into a persistent state. C. pneumoniae DNA was demonstrated in peripheral blood mononuclear cells in only 5% of aortic valve stenosis patients and not in thoracic aortic aneurysm or aortic dissection patients, suggesting that the bacterium disseminated to the cardiovascular tissue long before the patient required surgery. The copper/zinc ratio in serum, a marker of infection/inflammation, was significantly elevated in thoracic aortic aneurysm patients, supporting an inflammatory pathogenesis. Patients positive for C. pneumoniae in the aortic valve had more advanced coronary atherosclerosis, further supporting a possible role for C. pneumoniae in atherosclerosis. Mice were infected with C. pneumoniae that disseminated to all organs investigated (i.e. lungs, heart, aorta, liver and spleen). Trace element concentrations were altered in infected animals with an increased copper/zinc ratio in serum, a progressively increased iron concentration in the liver and a progressively decreased iron concentration in serum. Iron is important for C. pneumoniae metabolism, and a changed iron homeostasis was noted in infected mice by alterations in iron-regulating proteins, such as DMT1 and hepcidin

Reduced responsiveness of cutaneous microcirculation in essential hypertension - A pilot study

Objective. Our hypothesis states that the reactivity of the cutaneous microcirculation is reduced in patients with hypertension compared with healthy subjects. The objective was to verify the hypothesis by measuring microvascular function in hypertensive patients. Design. The study was a controlled trial with two arms: 15 hypertensives and 15 normotensives were enrolled, aged 30-60 years, and in hypertensives, a diastolic blood pressure of > 90 mmHg. The hypertensive patients were compared with gender- and age-matched controls having a diastolic blood pressure < 90 mmHg. The patients were kept on their medication. Method. The local cutaneous forearm blood flow was measured by Laser-Doppler flowmetry. The blood flow response to local warming (44 degrees C), to the endothelium-dependent vasodilator acetylcholine (ACh), or to the endothelium-independent dilators sodium nitroprusside (SNP) and calcitonin gene-related peptide (CGRP) administered by iontophoresis were determined. Inflammatory markers and NT-pro brain natriuretic peptide (NT-proBNP) levels in plasma was also measured. Electrocardiograms (ECG) were evaluated and the subjects answered a lifestyle questionnaire. Results. The percentage change in vasodilator response to CGRP was significantly lower in the hypertensives compared with normotensives, 285% (95% CI 86-484) vs 764% (95% CI 366-1162) of baseline, p < 0.05. The change to local warming was 2191% (95% CI 1574-2807) in normotensives vs 1384% (95% CI 852-1917) in the hypertensives, p < 0.05. The vasodilator response to ACh was 1249% (95% CI 895-1602) in the normotensives and 873% (95% CI 610-1136) in the hypertensives. The vasodilator response to SNP in the normotensives was 771% (95% CI 436-1107) and 682% (95% Cl 416-948) in the hypertensive group. Plasma level of NT-proBNP was 90 ng/l (95% CI 35-145) in normotensives vs 285 ng/l (95% CI 70-499) in hypertensives (p=0.06). The ECGs showed a tendency towards left ventricular hypertrophy (LVH) in hypertensives. Conclusion. Patients with essential hypertension had significantly reduced microvascular dilator responses to CGRP and to local warming. Also, there was a tendency towards reduced responses to ACh. This points towards a generally weaker responsiveness of the cutaneous microvessels in hypertensives and could be a contributing factor to the development of high blood pressure. Patients with essential hypertension also had a tendency of higher plasma levels of NT-proBNP, which could be seen as an early sign of organ damage

Det stora steget : - en studie om samverkan vid övergång från förskola till förskoleklass

De barn som befinner sig i förskolan kommer att få uppleva övergången mellan förskola och förskoleklass. Det är barnet som tar steget in i den nya verksamheten, vilket innebär att barnet är i centrum. Syftet med studien är att lyfta barns, föräldrars och pedagogers upplevelser kring samverkan samt hur pedagogerna arbetar med samverkan vid övergång mellan de olika verksamheterna. Upplevelserna sätts i relation till tidigare forskning och styrdokumentens skrivningar. Studiens syfte grundar sig på frågorna: Hur upplever/upplevde barnet övergången från förskola till förskoleklass? Hur upplever föräldrar och pedagoger samverkan vid övergång från förskola till förskoleklass? Vilka uttrycksformer har samverkan i verksamheterna? Studiens utformning grundar sig i en kvalitativ metod och det har genomförts barnintervjuer, föräldra- och pedagogenkäter med öppna frågor där deras upplevelser kring samverkan beskrevs på ett detaljrikt och djupgående sätt. Resultatet av studien synliggör att barnen upplever/upplevde övergången med stor glädje och förväntan. Barnen i förskolan visar på att de kommer känna en stor saknad av pedagoger och kamrater i förskolan. Föräldrarna och pedagogerna upplever samverkan som en betydelsefull process för det enskilda barnet. Föräldrarna lägger stort fokus på att barnet ska få inblick i den nya miljön, möta pedagogen samt de blivande kamraterna. Pedagogerna anser att samverkan skall utformas på ett gynnsamt sätt för barnet, men det framkommer att det finns ett flertal olika hinder som exempelvis riktlinjer, tid och geografiskt läge för att uppnå en tillfredställande samverkan. Det har lett till att samverkans uttrycksformer skiljer sig betydligt mellan de olika verksamheterna som ingår i studien

Reduced peripheral vascular reactivity in refractory angina pectoris: Effect of enhanced external counterpulsation

To examine if the skin microvascular bed is altered and can be modified by enhanced external counterpulsation (EECP) in patients with chronic refractory angina. Methods Twenty patients diagnosed with refractory angina were divided into EECP (n = 10) or no EECP (n = 10) groups. The data were compared to matched healthy subjects (n = 20). The cutaneous forearm microvascular blood flow was measured by Laser-Doppler flowmetry. The vascular responsiveness to iontophoretic administration of acetylcholine (ACh), sodium nitroprusside (SNP) and local skin warming were studied. Measurements of Canadian Cardiovascular Society (CCS)-class, blood pressure and plasma samples were registered. Results EECP patients showed reduced CCS-class compared to no EECP (P < 0.05). Both EECP and no EECP (P < 0.05) groups had decreased systolic blood pressure (SBP) as compared to SBP at baseline (P < 0.05). There was no difference in resting blood flow between the two refractory groups at baseline as well as after EECP and seven weeks of follow-up. Responses to heating, the responses to ACh and SNP in the cutaneous microcirculation were lower in both groups of refractory angina patients as compared to healthy subjects (P < 0.05). EECP patients corresponded positively to the treatment shown by reduced plasma level of soluble interleukin-2 receptor and CCS-class. Conclusions Refractory angina patients have reduced responsiveness in their cutaneous microcirculation to ACh, SNP and heat compared to healthy subjects. Although EECP reduced the CCS-class, this effect was not associated with improvements in responsiveness of the cutaneous microcirculation