Effects of a Pure α/β-Adrenergic Receptor Blocker on Monocrotaline-Induced Pulmonary Arterial Hypertension With Right Ventricular Hypertrophy in Rats

Background: It is unclear how Much the sympathetic nervous system is involved in the development of pulmonary arterial hypertension (PAH). The present study examined whether or not a pure alpha/beta-adrenergic receptor blocker (arotiriolol) could prevent the development of PAH and right ventricular hypertrophy (RVH) in a rat model of monocrotaline (MCT)-induced PAH. Methods and Results: The heart rate, arterial blood pressure (BP), left ventricular pressure, pulmonary artery pressure (PAP), and right ventricular pressure (RVP) were measured after administration of arotinolol or saline for 2 weeks. Ventricular weight and myocyte size were also measured. Mean PAP was increased less in the arotinolol group (n=6), (53+/-9 vs 21+/-2 mmHg in the control (n=6); P<0.01). Systolic RVP was also less in the arotinolol group (41+/-3 vs 91+/-14 mmHg in the control, P<0.05) without differences in BP. It also significantly reduced the RV/body weight ratio (0.58+/-0.01 vs 0.77+/-0.04 mg/g; P<0.01). Furthermore, the myocyte width was significantly decreased in the arotinolol group. Conclusions: The pure alpha/beta-blocker arotinolol prevented the progression of MCT-induced PAH and RVH in rats, suggesting that sympathetic nervous activation might play a role in the development of PAH. (Circ J 2009; 73: 2337-2341)