Heart failure (HF) is an inability to reach a cardiac output sufficient for the body’s metabolic demands. Following an initial insult (e.g. pressure overload), maladaptive remodelling of the myocardium takes place. One of the main elements of this is a desensitisation of the β-adrenergic response (secondary to an increase in sympathetic drive) which is characterised by decreased β1-adrenoceptor (β1AR) expression and receptor uncoupling. β-blockers are routinely used in the treatment of left ventricular (LV) HF and promote re-sensitisation of the β1AR as well as inhibiting pathways that lead to adverse remodelling. In patients with pulmonary artery hypertension (PAH), leading to right ventricular (RV) hypertrophy and failure, β-blockers are not usually prescribed. We examined whether a selective β1AR blocker metoprolol could show similar re-sensitisation of β1AR when treating RV HF induced by PAH. Male Wistar rats (180-220g) received an i.p. injection of saline (CON group) or 60 mg/kg of monocrotaline (MCT). MCT animals were given a selective β1AR blocker (10 mg/kg metoprolol; MCT+BB group) or placebo (MCT group) daily by oral administration from 15 days post injection. MCT induces RV hypertrophy which progresses to RV HF by 21-28 days post-injection when clinical symptoms are apparent (e.g. weight loss). MCT+BB and CON animals were time-matched to MCT animals; all rats were humanely killed. Langendorff-perfused hearts were used for ventricular myocyte isolation (for functional experiments) or preparation of myocardial homogenates (for protein expression via Western blotting). RV myocytes from MCT animals showed a blunted increase in fractional shortening to selective β1AR stimulation compared with CON (P<0.05; n=5-20; one-Way ANOVA). This difference was absent in MCT+BB cells (P>0.05; n=9). MCT myocytes also showed a slower time to 50% relaxation with selective β1AR stimulation compared with CON (P<0.05). Again this difference was absent in cells from MCT+BB. A similar trend was seen in Ca2+ transient amplitude and decay. Together this suggests a stepped improvement in β-AR responsiveness with metoprolol treatment. Myocardial β1AR expression was reduced in MCT vs. CON (P<0.05; n=5), but this effect was absent in MCT+BB (P>0.05; n=3). This graded improvement in β1-AR responsiveness with metoprolol treatment may come in part from the observed increase in myocardial β1AR expression. These results showing an improvement in function, along with other studies showing cardioprotective effects 1, provide support for the beneficial outcomes of treatment with selective β1AR blockers in RV failure. Small observational clinical trials2 have seen no increase in mortality risk with PAH patients already taking β-blockers. The exact molecular mechanism by which this reverse remodelling is achieved still requires further investigation.