Effects of heme-l-arginate on L-NAME-induced hypertension
N-ω-nitro-L-arginine methyl ester (L-NAME) has been used to induce experimental essential hypertension characterized by stimulation of the renin-angiotensin system (RAS) and oxidative system. Although the heme oxygenase (HO) system is known to suppress hypertension and the RAS, its effects on L-NAME-induced hypertension are poorly understood. Therefore, this study investigates the effects of heme-L-arginate (HA), a HO inducer, on L-NAME induced hypertension. HA (15mg/kg/day) was administered for 4 weeks either during the development or after the establishment (4 weeks) of L-NAME-induced (60mg/kg/day) hypertension in Sprague-Dawley (SD) rats. Vehicle control groups were used. Co-treatment with HA prevented the development of L-NAME induced hypertension, (124 mmHg, n=13 vs 168; n=10, 11 weeks; p<0.05). After L-NAME-induced hypertension was established for 4 weeks, HA therapy reduced blood pressure to normotensive at 15 weeks (123 mmHg, n=8 vs. 190 mmHg, n=7; (p<0.01). The prevention of hypertension was associated with increased HO-1 expression at 11 weeks (92.2±9.8 vs 15.9±9.9 HO-1/GAPDH %, n=4; p<0.01), reduction of heart Ang-II at 11 and 15 weeks (2.13±0.4 pg/mg, n=6 vs 4.06±0.4 pg/mg, n= 8; p<0.05 and 3.45±0.2 pg/mg, n=7 vs 4.23±0.2, n=7; p<0.05), respectively. HA co-treatment increased total antioxidant capacity (TAC) in heart tissue, the mesenteric artery and kidney. We conclude that up-regulating the HO system with HA normalizes blood pressure and prevents the development of L-NAME induced hypertension by suppressing Ang-II and abating oxidative stress. HA may be explored in the prevention and management of other forms hypertension characterized by elevated Ang-II and excessive oxidative stress.
DegreeMaster of Science (M.Sc.)
SupervisorNdisang, Joseph F.
CommitteeDesautels, Michel; West, Nigel; Alcorn, Jane
Copyright DateAugust 2012
N-ω-nitro-L-arginine methyl ester