We immunized our animals against the second extracellular loop of a1A-AR. This report is the first showing the in vivo relevance of a1A-AR-AB to our knowledge. We investigated the effects on blood pressure by radiotelemetry and on Alosetron Cardiac function by invasive hemodynamic measurements with a conductance catheter and echocardiography. Cardiac molecular pathways influenced by a1A-AR-AB signaling were investigated by gene expression array analyses. Furthermore, we tested the hypothesis whether immunized rats react more sensitive to angiotensin II. The immunized rats developed specific a1A-AR-AB that we detected by both cardiomyocyte contraction assay and ELISA. The blocking experiments underscored the specificity of these antibodies. The antibodies were capable of initiating a1A-AR signaling as documented by our phospho-ERK1/2 experiments. We documented clear-cut differences in cardiac function by two independent techniques, one relying on direct cardiac catheterization that revealed a diastolic pathology. Cardiac structure was substantially different between the groups, as shown by echocardiography and by light microscopy. Our notion that a much more sensitive blood pressure measurement than the tail-cuff technique would show a difference in blood pressure between groups, proved not to be the case. Nonetheless, the Ang II experiments showed clearly that when a driving force for hypertension is applied, the presence of a1A-AR-AB clearly aggravates target organ damage and blood pressure. Finally, we explored new mechanistic pathways. Our gene expression analyses showed different compensatory mechanisms in structure and metabolism to maintain the cardiac function. In contrast to the failing rat heart with a shift in myosin isoform from a to b-MHC, we found instead an increased expression of both MHC isoforms. Up-regulation of b-MHC transcription can serve as an early and sensitive marker of cardiac hypertrophy and may conserve energy. Dexmedetomidine HCl Forced expression of a-MHC may be beneficial in terms of increasing the myocardial contractility and may result in cardioprotection.