title: The asymmetric dimethylarginine-mediated inhibition of nitric oxide in the rostral ventrolateral medulla contributes to regulation of blood pressure in hypertensive rats.
abstract: Nitric oxide (NO) contributes to the central control of cardiovascular activity. The rostral ventrolateral medulla (RVLM) has been recognized as a pivotal region for maintaining basal blood pressure (BP) and sympathetic tone. It is reported that asymmetric dimethylarginine (ADMA), characterized as a cardiovascular risk marker, is an endogenous inhibitor of nitric oxide synthesis. The present was designed to determine the role of ADMA in the RVLM in the central control of BP in hypertensive rats. In Sprague Dawley (SD) rats, microinjection of ADMA into the RVLM dose-dependently increased BP, heart rate (HR), and renal sympathetic never activity (RSNA), but also reduced total NO production in the RVLM. In central angiotensin II (Ang II)-induced hypertensive rats and spontaneously hypertensive rat (SHR), the level of ADMA in the RVLM was increased and total NO production was decreased significantly, compared with SD rats treated vehicle infusion and WKY rats, respectively. These hypertensive rats also showed an increased protein level of protein arginine methyltransferases1 (PRMT1, which generates ADMA) and a decreased expression level of dimethylarginine dimethylaminohydrolases 1 (DDAH1, which degrades ADMA) in the RVLM. Furthermore, increased AMDA content and PRMT1 expression, and decreased levels of total NO production and DDAH1 expression in the RVLM in SHR were blunted by intracisternal infusion of the angiotensin II type 1 receptor (AT1R) blocker losartan. The current data indicate that the ADMA-mediated NO inhibition in the RVLM plays a critical role in involving in the central regulation of BP in hypertension, which may be associated with increased Ang II.
authors.affiliation: Department of Physiology and Center of Polar Medical Research, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Physiology and Center of Polar Medical Research, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Ji-Kui
authors.initials: JK
authors.lastname: Li
authors.affiliation: Department of Physiology and Center of Polar Medical Research, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Jia-Cen
authors.initials: JC
authors.lastname: Sun
authors.affiliation: Department of Physiology and Center of Polar Medical Research, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Pei-Lei
authors.initials: PL
authors.lastname: Jiao
authors.affiliation: Department of Physiology and Center of Polar Medical Research, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Yang-Kai
authors.initials: YK
authors.lastname: Wang
authors.affiliation: Department of Physiology and Center of Polar Medical Research, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Zhao-Tang
authors.initials: ZT
authors.lastname: Wu
authors.affiliation: Department of Physiology and Center of Polar Medical Research, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Physiology and Center of Polar Medical Research, Second Military Medical University, Shanghai, 200433, China. Electronic address: wangwz68@hotmail.com.
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Wang
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; C541817:PRMT1 protein, rat; D011484:Protein-Arginine N-Methyltransferases; D000581:Amidohydrolases; C059999:dimethylargininase; D019808:Losartan
keywords: ADMA; Angiotensin II; Hypertension; Nitric oxide; RVLM