The present investigation was carried out to study the antihypertensive activity of the two derivatives (NS1 & NS2) of novel synthetic hybrid compound [N(phenyl)N′{1′6methyl-4-(2-nitrophenyl)-2-thioxo- 1,2,3,4-tetrahydropyrimidine- 5- carboxylic acid ethyl ester} 3′ (4″ imino phenoxy) propane-2- ol thiourea] on 2K1C induced hypertensive rats. The left renal artery (LRA) was ligated by silk suture (no.4) in rats to produce two-kidney one-clip (2K1C) renovascular hypertension and kept for 6 weeks. After 6 weeks, respective treatments were started and continued for 7 days. On 7th day, 30 min after the last dose, the arterial blood pressure and heart rate (HR) of rats were measured by using data acquisition system. LRA ligated rats showed significant (P < 0.01) increment in mean arterial pressure (MAP) compared to non-ligated (normal) rats. NS1 decreased MAP and HR significantly (P<0.01) while NS2 significantly (P<0.01) decreased MAP without affecting heart rate when compared against LRA ligated rats. Standard drugs were significant (P<0.01) in reducing MAP as well as HR of LA ligated rats. In conclusion, both the derivatives (NS1 and NS2) of the novel synthetic hybrid compound showed significant reduction in the blood pressure of 2K1C induced hypertensive rats, while HR was only significantly reduced by NS1. The study needs further investigation to know the exact mechanism of antihypertensive activity of these hybrid compounds.