Heart failure (HF) is a major health problem affecting nearly 1 million people in the UK today. The mechanisms which underlie its progression are not fully understood. A hallmark of remodelling in the failing heart is a desensitisation of the β-adrenoceptor (AR) signalling pathway, associated with aberrant spatial control of cAMP. Caveolae, flask-shaped lipid rafts, are key controllers of β-AR signalling [1]. Many of the proteins involved in the β-AR cascade are present in caveolar domains or interact with caveolin. Here we determine whether caveolar remodelling occurs in a model of right ventricular (RV) HF caused by pulmonary hypertension. Male Wistar rats (190-230g) received an i.p. injection of 60 mg/kg monocrotaline (MCT) or saline (CON). MCT induces RV hypertrophy which progresses to RV HF by 21-28 days post-injection. When clinical symptoms of HF were apparent, the heart was quickly excised and the coronary circulation cleared of blood on a Langendorff apparatus. The RV was homogenised in detergent-free buffer (500mM Na2CO3 with protease inhibitor cocktail) then sonicated. Samples were mixed with Laemmli sample buffer for Western blotting to assess total protein expression, or separated on a discontinuous sucrose gradient [1] to assess protein distribution. Proteins of interest include caveolar proteins caveolin (Cav) 1, Cav3 and cavin 1 which are crucial for caveolar formation, and components of the β-AR cascade (β1-AR, β2-AR and adenyly cyclase (AC) 5/6). As shown in Fig. 1A, expression of all caveolar proteins and both β1 and β2-ARs was decreased in MCT rats compared with CON (P<0.01, t-test). AC 5/6 expression was not affected by HF. Cav3 is the major caveolar protein in the cardiac myocyte. Following sucrose density gradient fractionation, caveolae-containing membranes (indexed by enrichment in Cav3) are typically found in fraction 5 and 6 which we designate the buoyant fractions (BF). Fig. 1B shows that the distribution of Cav3 in the membrane is perturbed by RV failure. The ratio of Cav3 in BF to heavy fractions (HFr;9-12) was significantly reduced in MCT rats compared with CON (P<0.05, t-test). Together the finding of decreased expression of caveolar proteins along with a translocation of Cav3 from caveolar fractions is consistent with a disruption of the caveolar microdomain. These changes are likely to impact on both the basal function and AR responses of the myocyte. We consider that a better understanding of the changes which occur in the caveolar domain could lead to identification of possible pharmacological targets for reverse remodelling of the βAR pathway in HF.