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Dyxin is a LIM-domain containing transcriptional regulator protein shown to play a role in a hypertrophic response in the heart. Here, the effect of adenoviral dyxin overexpression was studied on cardiac function and gene expression in the normal heart and in angiotensin II (Ang II)-induced hypertension in rats. The adenovirus-mediated intramyocardial gene transfer of dyxin (1.5×109 infectious units/animal) was performed into the left ventricle (LV) of Sprague-Dawley rats with and without the Ang II (33 µg/kg/h) infusion, administered via osmotic minipumps for 1 and 2 weeks. Echocardiography was used to assess the structural and functional changes. Dyxin expression and localization in the heart was analyzed with quantitative RT-PCR and immunohistochemistry, respectively. In the normal rat heart, the adenoviral overexpression of dyxin did not alter LV function in normal hearts as assessed by echocardiography. Dyxin was found to be localized in the cardiomyocytes as shown by the immunohistochemical staining. In Ang II-induced hypertrophy, echocardiographic data revealed a significant increase in the posterior wall diameter both in systole (21%, P<0.05) and diastole (21%, P<0.01) as well as in the diameter of the interventricular septum in systole (19%, P<0.05) in the dyxin-injected group compared with the LacZ-injected animals after two weeks of Ang II infusion. Interestingly, a significant decrease in the levels of both atrial natriuretic peptide (ANP) mRNA (55%, P<0.01) and B-type natriuretic peptide (BNP) mRNA (68%, P<0.05) was observed in the dyxin-injected group compared with the LacZ control group after one week of Ang II infusion. These results indicate that dyxin overexpression was deteriorative against pressure overload by inducing structural changes in the LV in rats. Interestingly, simultaneous adenoviral overexpression of dyxin suppressed the Ang II-induced changes of ANP and BNP genes suggesting that dyxin might have a role as a regulator of the cardiac hypertrophic gene program. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is linked to premature mortality of virtually all causes. Furin is a proprotein convertase broadly involved in the maintenance of cellular homeostasis; however, little is known about its role in the development of diabetes mellitus and risk of premature mortality.Objectives: To test if fasting plasma concentration of furin is associated with the development of diabetes mellitus and mortality.Methods: Overnight fasted plasma furin levels were measured at baseline examination in 4678 individuals from the population-based prospective Malmö Diet and Cancer Study. We studied the relation of plasma furin levels with metabolic and hemodynamic traits. We used multivariable Cox proportional hazards models to investigate the association between baseline plasma furin levels and incidence of diabetes mellitus and mortality during 21.3-21.7 years follow-up.Results: An association was observed between quartiles of furin concentration at baseline and body mass index, blood pressure and plasma concentration of glucose, insulin, LDL and HDL cholesterol (|0.11| ≤ β ≤ |0.31|, P < 0.001). Plasma furin (hazard ratio [HR] per one standard deviation increment of furin) was predictive of future diabetes mellitus (727 events; HR = 1.24, CI = 1.14-1.36, P < 0.001) after adjustment for age, sex, body mass index, systolic and diastolic blood pressure, use of antihypertensive treatment, alcohol intake and fasting plasma level of glucose, insulin and lipoproteins cholesterol. Furin was also independently related to the risk of all-cause mortality (1229 events; HR = 1.12, CI = 1.05-1.19, P = 0.001) after full multivariable adjustment.Conclusion: Individuals with high plasma furin concentration have a pronounced dysmetabolic phenotype and elevated risk of diabetes mellitus and premature mortality. [ABSTRACT FROM AUTHOR]

The activity on α-adrenoreceptors of medetomidine (±)-4-(α,2,3-trimethylbenzyl)imidazole), an α-methyl derivative of detomidine, has been characterized in vivo and in vitro using detomidine, MPV 207, MPV 295, azepexole, clonidine and xylazine for reference purposes., Medetomidine (1-100 μg/kg i.v.) was a hypotensive and bradycardic compound in anaesthetized rats. Furthermore, it induced vasopressor (PD50 1.7 μg/kg) and sympatho-inhibitory (ID50 1.6 μg/kg) actions in pithed rats, the effects being antagonized by idazoxan (0.3 mg/kg i.v.) but not by prazosin (0.1 mg/kg i.v.). Medetomidine (30-300 μg/kg i.m.) had an α2-adrenoreceptor mediated sedative effect on chicks., Medetomidine was, overall, more potent than detomidine, MPV 207, clonidine, xylazine, MPV 295 or azepexole in central (sedation in the chick) and peripheral (cardiac presynaptic in the pithed rat) actions on α2-adrenoreceptors. Clonidine had, however, about an equal potency to medetomidine in the vascular smooth muscle of the pithed rat., Like detomidine and MPV 295, medetomidine had no agonistic activity in the rat aortic ring, but high concentrations antagonized methoxamine-induced contractions, giving a pA2 value of 5.68 for α1-adrenoreceptor antagonism., The overall lipophilicity (log P') of medetomidine in the octanol/buffer (pH 7.4, 24-26°C, HPLC technique) was 2.80., In summary, the experimental data suggest that medetomidine is a lipophilic compound with selective α2-adrenoreceptor-stimulating properties and high potency. It may, therefore, prove to be a suitable pharmacologic tool for interventions in α2-adrenoreceptor mediated effects in the autonomic nervous system. [ABSTRACT FROM AUTHOR]

The inter-relationships between ischaemia-induced metabolic changes and atrial natriuretic peptide (ANP) release were studied in 18 patients undergoing elective percutaneous transluminal coronary angioplasty (PTC A). Transcardiac differences in ANP, lactate, pH, pCO and O saturation were analysed before and after balloon inflation. The patients were divided into ischaemia and non-ischaemia groups on the basis of the change in lactate extraction ratio during balloon inflation. The ischaemia group (patients with a decrease in lactate extraction ratio) showed an increase of 27±15 pg. ml in the transcardiac ANP difference, whereas a decrease of 27±17pg.ml occurred in the non-ischaemia group (no decrease in lactate extraction ratio). The change between the two patient groups was statistically significant (<0.05). Metabolic ‘pre-conditioning’ was not observed in (P<0.05) was obtained between the PTCA-induced changes in transcardiac ANP and lactate differences. We conclude that transient myocardial ischaemia induced by PTCA increases circulating ANP concentrations in patients with signs of metabolic ischaemia, but not in those without. [ABSTRACT FROM PUBLISHER]

Mammalian atrial cardiocytes synthesize and secrete a hormone called atrial natriuretic peptide (ANP), which causes natriuresis, diuresis and inhibition of smooth muscle contraction, aldosterone and renin release. Volume loading, vasoconstrictor agents, immersion in water, atrial tachycardia and high salt diets have been reported to increase the release of cardiac ANP, thereby suggesting that the peptide is released in response to an increase in atrial pressure. That stretch is an important stimulus for ANP release is also suggested by clinical studies demonstrating a direct correlation between secretion rate and atrial pressure. The experiments using isolated perfused rat heart provide direct evidence that distension of the right atrium stimulates the release of ANP. Pharmacological studies in the isolated heart point to roles of cytosolic calcium, the phosphoinositide system and the cyclic AMP pathway in the regulation of ANP release. The concentration of calcium in heart muscle cells, in addition to the length of the muscle fibers, depends on many factors such as the action of humoral substances, cardiac nerve activity and heart rate, which may all contribute to the regulation of ANP secretion. [ABSTRACT FROM PUBLISHER]

An abstract of the study "P38 Kinase Rescues Failing Myocardium After Myocardial Infarction: Evidence for Angiogenic and Anti-Apoptotic Mechanisms," by O. Tenhunen and colleagues is presented.

Presents summaries of symposiums on the evaluation of heart failure in Scandinavia. Characterization of Natriuretic peptides; Utilization of the peptides as markers of cardiac function; Description of low-density lipoproteins fractions by dynamic laser light scattering.

Background: Risk stratification for cardiovascular outcomes is gaining importance in general population. Prognostic value of natriuretic peptides has been established in patients with heart failure. However, the prognostic significance of natriuretic peptides with respect to stroke is not well known in general populations. Methods: Plasma natriuretic peptides were measured in a representative population-based sample of 958 men (age 46-65 years) from Eastern Finland. There were 46 cases of stroke, 74 of atrial fibrillation and 31 cases of ischaemic strokes during a follow-up of 9.6 years. Results: The multivariable adjusted risk was 1.35-fold (95% CI 1.01 to 1.84, p = 0.049) for any stroke and 1.30-fold (95% CI 0.90 to 1.91, p = 0.0150) for ischaemic stroke for each log-transformed SD (0.240 pmol/l) increment in N-terminal fragment of proA-type natriuretic peptide. The respective risks were 1.36-fold (95% CI 1.05 to 1.76, p = 0.010) and 1.50-fold (95% CI 1.12 to 2.02, p = 0.007) for each log-transformed SD (0.237 pmol/l) increment in N-terminal fragment of proB-type natriuretic peptide. The multivariate adjusted risks for future atrial fibrillation were 1.71 (95% CI 1.32 to 2.22, p<0.001) and 1.68-fold (95% CI 1.38 to 2.07, p<0.001) for each log-transformed SD increment in N-terminal fragments of proA- and proB-type natriuretic peptides, respectively. Conclusions: N-terminal fragments of pro-atrial natriuretic peptide and pro-brain natriuretic peptide are new additional predictors of any stroke and atrial fibrillation. Natriuretic peptides provide prognostic information for stroke and atrial fibrillation and may help in identifying subjects at risk for stroke and atrial fibrillation. [ABSTRACT FROM AUTHOR]

An abstract of the study "Distinct Down-Regulation of C-Type Natriuretic Peptide System in Human Aortic Valve Stenosis," by J. Rysa and colleagues is presented.

An abstract of the study "Melusin gene expression in the heart: The role of mechanical load and hypertrophic agonists," by J. Aro and colleagues is presented.

An abstract of the study "Vasoactive peptide and interleukin-6 levels in relation to indices of left ventricular remodeling and performance in patients with idiopathic dilated cardiomyopathy," by E. Saastamoinen et al, is presented.