Heart failure (HF) is a major health problem in the UK today which puts a major burden on the NHS. A hallmark of HF is a desensitisation in the β-adrenoceptor (β-AR) response, associated with aberrant spatial control of intracellular cAMP. Caveolae, flask-shaped invaginations of the plasma membrane, are key controllers of β-AR signalling. Many of the proteins involved in the β-AR cascade are present in caveolar domains or interact with caveolar proteins. The molecular changes which occur to the β-AR cascade in HF are not yet fully understood. Using two different models of HF, one induced by pulmonary hypertension causing right ventricular (RV) pressure-overload and one induced via aortic banding causing left ventricular (LV) pressure-overload, we can begin to address these molecular changes in relation to the caveolae. RV HF model: Male Wistar rats (190-230g) received an i.p. injection of 60 mg/kg monocrotaline (MCT) or saline. MCT induces RV hypertrophy which progresses to RV HF by 21-28 days post-injection. LV HF model: Male Wistar rats (80 ± 20g) were anaesthetized through inhalation with isoflurane (3.5% in medical O2) and partial thoracotomy performed were a metal clip was (I.D=0.6mm) placed around the ascending aorta. Sham animals underwent identical surgery minus aortic banding. When ejection fraction (EF) fell >45% (19-26 weeks post-surgery), pressure-volume loops were measured under anaesthesia (as above). Sham animals were time matched. Ventricular muscle was homogenized in Laemmli sample buffer for Western blotting to assess total protein expression and homogenised in detergent-free buffer (500mM Na2CO3) and sonicated, then separated on a discontinuous sucrose gradient to assess protein distribution. Proteins of interest include caveolar proteins caveolin (Cav) 1, Cav 3, cavin 1 and cavin 4 which are crucial for caveolar formation. Figure 1 shows changes in expression of the caveolar proteins in the RV and LV HF models. There was a decrease in Cav 1, Cav 3 and Cavin 1 expression (P<0.01) and a trend for an increase in cavin 4 (P=0.2) in the RV HF model compared with controls. The proportion of Cav 3 and cavin 1 found in the buoyant caveolae containing fractions was also reduced in this model. In the LV model there was a decrease in Cav 1 and an increase in cavin 4 (P<0.05) compared with sham animals. For both models, the largest change was in Cav1 expression. Of note, Cav 1 expression has previously been seen to decreased in human HF and increased expression after mechanically unloading of the heart with a LV assisted device 1. Increased cavin 4 expression in the LV failure model reflects recent reports of a link between cavin 4 and hypertrophic signalling 2. Understanding the changes occurring in the controlled microenvironment of the caveolae in HF may aid in explaining the aberrant βAR signalling seen and reveal possible pharmacological targets.