ulmonary arterial hypertension (PAH) is a serious chronic disorder, similar to chronic kidney disease, which has varied causes and pathogenesis. PAH can potentially lead to right ventricular hypertrophy (RVH) and cardiovascular death related to RV failure. Among the types of PAH, idiopathic PAH has an especially poor prognosis and is difficult to manage clinically. Idiopathic PAH involves multiple factors, such as vasoconstriction, remodeling of the pulmonary vessels, and thrombosis, but it is unclear to what extent the sympathetic nervous activation plays a role in its development. Certainly, sympathetic nervous activity is reported to be increased in PAH; 1 however, it is unclear whether or not inhibition of sympathetic activity can prevent or reverse PAH. The benefits of inhibiting sympathetic nervous activation in PAH remain uncertain, although there have been several reports regarding the effects of α-and/or β-adrenergic receptor blockers, especially carvedilol, although it is not a pure α/ β-adrenergic receptor blocker. Arotinolol (Dainippon Sumitomo Pharma Co, Ltd, Osaka, Japan) is a nonselective α/ β-adrenergic receptor blocker lacking local anesthetic, membrane-stabilizing or intrinsic sympathomimetic properties, which means that arotinolol is a pure α/ β-adrenergic receptor blocker. 2,3
Editorial p 2212Therefore, we investigated whether or not arotinolol, which differs from carvedilol with regard to actions such as an antioxidant or calcium-channel blocking effect, 4,5 could prevent the development of PAH and/or RVH in a rat model of monocrotaline (MCT)-induced PAH.
MethodsThe experimental procedures described in the present study were approved by the institutional Animal Care and Use Committee of Nippon Medical School. Six-week-old male Wistar rats (n=12) were used. MCT was dissolved in 1 N HCl, and the pH was adjusted to 7.4 with 1 N NaOH. Rats were injected subcutaneously with 2% MCT solution at a dose of 40 mg/kg. An intraperitoneal osmotic pump (Alzet Osmotic Pumps, Durect, Cupertino, CA, USA) containing either arotinolol (0.25 mg · kg -1 · day -1 , n=6) or 0.9% saline (n=6) was implanted randomly under anesthesia induced by intraperitoneal injection of sodium pentobarbital (30 mg/kg). A previous study showed intraperitoneal administration of arotinolol has almost the same effects as intravenous administration. 6 We did preliminary experiments to decide the dose of arotinolol required to reduce blood pressure (BP) 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 α/ β-adrenergic receptor blocker (arotinolol) 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 week...