Journal of Clinical & Experimental Pharmacology

The pharmacodynamics evaluation of SGC-003, a novel soluble guanylate cyclase agonist, on pulmonary hypertension in rats

World Congress on Pharmacology

July 20-22, 2015 Brisbane, Australia

Yan Ling-Di, He Zong-Sheng, Dong Hua-jin, Su Rui-Bin, Gong Ze-Hui and Zhen Zhi-Bing

Posters-Accepted Abstracts: Clin Exp Pharmacol

Abstract:

Aim: The purpose of the present study is to evaluate the pharmacodynamics of SGC-003(Methyl-4,6-diamino-2-(1-(thien-2- yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-pyrimidin-5-ylmethylcarbamate), a novel soluble guanylate cyclase agonist, synthesized by Beijing Institute of Pharmacology and Toxicology on hypoxia and monocrotaline (MCT)-induced pulmonary hypertension in rats. Methods: The rats were exposed to chronic hypoxia (10% O2) in a ventilated chamber for three weeks or subcutaneously administrated monocrotaline (50 mg/kg) for two weeks to obtain Pulmonary Hypertension (PH) model. Pulmonary arterial pressure on anesthetized rats was measured by a blood pressure instrument. Results: In chronic treatment of hypoxia in rats, SGC-003 (0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg, i.g., twice/day for 3 weeks) significantly inhibited the increase in the mean pulmonary arterial pressure (MPAP) (P<0.05), right ventricle systolic pressure (RVSP) (P<0.001) and right ventricular hypertrophy index (RVHI) (P<0.01) in dose-dependent manner, compared with model group, with the ratio of inhibition being 25.10%, 68.15% and 35.45%, respectively. In chronic treatment of MCT-injected rats with fully established PH, SGC-003 (0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg, i.g., twice/day for 2 weeks) partially reversed the PH, with MPAP (P<0.05), RVSP (P<0.01) and RVHI (P<0.01), significantly decreasing in dose-dependent manner compared with model group with the ratio of inhibition being 59.82%, 55.20% and 30.19%, respectively. In addition, the experimental data from the noninvasive blood test indicated that systemic blood pressure did not significantly change after chronically administrating SGC-003 for eleven days. The above effects of SGC-003 were equivalent to BAY63-2521. Conclusion: SGC-003, a novel soluble guanylate cyclase agonist, has the inhibition effect on PH induced by hypoxia and MCT, which is equivalent to BAY63-2521.