N-acetylcysteine prevents hypertension via regulation of the ADMA-DDAH pathway in young spontaneously hypertensive rats.
Asymmetric dimethylarginine (ADMA) reduces nitric oxide (NO), thus causing hypertension. ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH), which can be inhibited by oxidative stress. N-Acetylcysteine (NAC), an antioxidant, can facilitate glutathione (GSH) synthesis. We aimed to determine whether NAC can prevent hypertension by regulating the ADMA-DDAH pathway in spontaneously hypertensive rats (SHR). Rats aged 4 weeks were assigned into 3 groups (n = 8/group): control Wistar Kyoto rats (WKY), SHR, and SHR receiving 2% NAC in drinking water. All rats were sacrificed at 12 weeks of age. SHR had higher blood pressure than WKY, whereas NAC-treated animals did not. SHR had elevated plasma ADMA levels, which was prevented by NAC therapy. SHR had lower renal DDAH activity than WKY, whereas NAC-treated animals did not. Renal superoxide production was higher in SHR than in WKY, whereas NAC therapy prevented it. NAC therapy was also associated with higher GSH-to-oxidized GSH ratio in SHR kidneys. Moreover, NAC reduced oxidative stress damage in SHR. The observed antihypertensive effects of NAC in young SHR might be due to restoration of DDAH activity to reduce ADMA, leading to attenuation of oxidative stress. Our findings highlight the impact of NAC on the development of hypertension by regulating ADMA-DDAH pathway.
Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Nai-Chia
NC
Fan
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Dabi Road, Niausung, Kaohsiung 833, Taiwan.
Chih-Min
CM
Tsai
Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan ; Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chien-Ning
CN
Hsu
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Dabi Road, Niausung, Kaohsiung 833, Taiwan.
Li-Tung
LT
Huang
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Dabi Road, Niausung, Kaohsiung 833, Taiwan ; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
You-Lin
YL
Tain
D000111:Acetylcysteine / Q000008:administration & dosage*; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D005978:Glutathione / Q000096:biosynthesis; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D053858:Metabolic Networks and Pathways; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase; D005978:Glutathione; D000111:Acetylcysteine