Abstract 329: Oral Administration of New Calcium Channel Antagonist Reverses Right Ventricular Dysfunction in Rats With Pulmonary Arterial Hypertension

Autor: Sharlene L Pereira, Allan K Alencar, Arthur E Kummerle, Emanuelle B Ferraz, José Nascimento, Carlos A Fraga, Eliezer J Barreiro, Roberto T Sudo, Gisele Zapata-Sudo
Rok vydání: 2012
Předmět:
Zdroj: Hypertension. 60
ISSN: 1524-4563
0194-911X
Popis: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, endothelial injury and vascular remodeling, right ventricular hypertrophy and increased right ventricular systolic pressure. This work investigated the effects of LASSBio-1289, a new calcium channel antagonist, in rats with PAH induced by monocrotaline (MCT). METHODS: Male Wistar rats (200 - 250 g) received a single MCT i.p. injection (60 mg/kg) for induction of PAH. The experimental groups were: control, MCT, MCT + vehicle, MCT + LASSBio-1289 (50 mg/kg p.o.). Animals were treated either with vehicle or LASSBio-1289 for 14 days after the onset of disease. The following parameters were analyzed: right ventricular systolic pressure (RVSP), RV contractility (dp/dtmax), RV relaxation (dp/dtmin)and RV weight / left ventricle + septum weight (RV/LV+S). Echocardiography was performed to determine RV area and wall thickness. The protocols used in the present study were approved by Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Results: RVSP (mmHg) increased from 25.3 ± 1.9 (control) to 49.0 ± 6.2 (P < 0.05) and 52.7 ± 6.2 (P < 0.05) in MCT and MCT + vehicle groups, respectively. When MCT-injected rats were treated with LASSBio-1289, RVSP was decreased to 36.4 ± 2.0 mm Hg (P < 0.05). RV/LV+S increased from 0.24 ± 0.02 to 0.56 ± 0.04 (P < 0.05) and 0.49 ± 0.03 in the MCT and MCT + vehicle groups (P < 0.05) and reduced to 0.30 ± 0.03 (P < 0.05) after treatment with LASSBio-1289. The dp/dtmax (mmHg/s) was 1179 ± 137, 2180 ± 238, 2482 ± 371 and 1134 ± 131 for control, MCT, MCT + vehicle and MCT + LASSBio-1289 groups. In addition to this, the dp/dtmin (mmHg/s) increased from -702 ± 83 to -1359 ± 120, -1720 ± 243 in the MCT and MCT + vehicle groups. In contrast, treatment with LASSBio-1289 reduced this parameter to -701 ± 122 (P < 0.05). RV area (mm2) was increased from 8.2 ± 0.5 to 17.8 ± 1.4 and 18.7 ± 1.0 in the PAH groups. RV area was reduced in LASSBio-1289-treated rats to 9.4 ± 0.9 (P < 0.05). PAH increased the RV wall thickness (cm) from 0.089 ± 0.002 to 0.125 ± 0.006 (P < 0.05) and was reduced to 0.098 ± 0.006 after treatment with LASSBio-1289. Conclusions: LASSBio-1289 effectively reversed right ventricular dysfunction and hypertrophy in rats with monocrotaline-induced PAH.
Databáze: OpenAIRE
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