Background-The signaling cascades responsible for the activation of transcription factors in the hypertrophic growth of cardiac myocytes during hemodynamic overload are largely unknown. Several of the genes upregulated in the hypertrophied heart, including B-type natriuretic peptide (BNP) gene, are controlled by the cardiac-restricted zinc finger transcription factor GATA4. Methods and Results-An in vivo model of intravenous administration of arginine 8 -vasopressin (AVP) for up to 4 hours in conscious normotensive rats was used to study the signaling mechanisms for GATA activation in response to pressure overload. Gel mobility shift assays were used to analyze the trans-acting factors that interact with the GATA motifs of the BNP promoter. AVP-induced increase in mean arterial pressure was followed by a significant increase in the BNP and c-fos mRNA levels in both the endocardial and epicardial layers of the left ventricle, whereas GATA4 and GATA6 mRNA levels remained unchanged. Pressure overload within 15 to 60 minutes produced an increase in left ventricular BNP GATA4 but not GATA5 and GATA6 binding activity, and at 30 minutes a 2.2-fold increase (PϽ0.001) in GATA4 binding was noted. The mixed endothelin-1 ET A /ET B receptor antagonist bosentan but not the angiotensin II type 1 receptor antagonist losartan completely inhibited the pressure overload-induced increase in left ventricular BNP GATA4 binding activity. Bosentan alone had no statistically significant effect on GATA4 binding activity of the left ventricle in conscious animals. Conclusions-ET-

The present results show that, during pressure overload and compensated left ventricular hypertrophy, the expression of BK-2Rs is increased. However, ongoing pressure overload leads to a loss of BK-2Rs with a dramatic increase in left ventricular fibrosis followed by diastolic dysfunction and heart failure.

AimTo evaluate the applicability of imaging devices (spectral-domain optical coherence tomography (Cirrus SD-OCT), scanning laser polarimetry (GDx) and scanning laser ophthalmoscopy (Heidelberg Retinal Tomograph, HRT3)) for glaucoma screening in a middle-aged unselected population.MethodsParticipants of the population-based Northern Finland Birth Cohort Eye Study, aged 45 to 49 years, underwent a comprehensive eye examination including modern imaging with five methods (retinal nerve fibre layer (RNFL) and macular ganglion cell layer +inner plexiform layer (GCIPL) analysis and their combination with SD-OCT, GDx and HRT). The performance of the automated classification of the imaging devices was assessed using a clinical glaucoma diagnosis as reference, that is, the ‘2 out of 3’ rule based on the evaluation of optic nerve head and RNFL photographs and visual fields.ResultsWe examined 6060 eyes of 3039 subjects; in the clinical evaluation, glaucomatous damage was found in 33 subjects (1.1%) in 43 eyes. The following sensitivities were obtained; RNFL analysis (53%), GCIPL analysis (50%), OCT combination analysis (61%), GDx (56%) and HRT (31%) with corresponding specificities of 95%, 92%, 90%, 88% and 96%. The area under the curve values were 0.76, 0.73, 0.75, 0.75 and 0.73, respectively. Post-test probabilities of glaucoma after positive imaging finding with each of these methods in this unselected population were 11%, 7%, 6%, 5% and 7%, respectively.ConclusionScreening capabilities of the OCT, GDx and HRT were rather similar. The accuracy of all evaluated parameters was only moderate and thus screening with these parameters alone is not reliable.

Individual and permanent identification of experimental animals is a common and often essential research practice. There is little information available on the short-term effects of these procedures on the animals. In this study, seven rats were implanted with telemetric devices. The effects of three different identification methods (ear tattoo, ear notching and microtattoo) were compared. Cardiovascular data were collected for 24 h after the procedures. Time periods of 0-1, 1-4, 4-16 h (dark) and 16-24 h after the procedure were analysed separately. The most pronounced differences in measured parameters were observed during the first hour after the procedures were performed. Mean arterial pressure (MAP) was significantly higher (P < 0.012) following the ear tattoo than the microtattoo procedure by a difference of approximately 5 mmHg. Heart rate (HR) was significantly elevated (P < 0.001) after ear tattoo compared with both ear notching (Δ = 31 beats per minute [bpm]) and microtattoo (Δ = 44 bpm). During the 1-4 h period and the following dark period, the MAP was highest in the ear notching group, but no differences were observed in the HRs. During the following dark period (4-16 h) and the next day (16-24 h) differences in MAP and HR were minor. In conclusion, microtattoo appears to cause the mildest changes in HR and blood pressure. Based on these results, ear tattoo and ear notching should be replaced by microtattoo whenever possible.