Decrease in the synthesis and release of calcitonin gene-related peptide in dorsal root ganglia of spontaneously hypertensive rat: role of nitric oxide synthase inhibitors.
Calcitonin gene-related peptide (CGRP), the major transmitter in capsaicin-sensitive sensory nerves, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, participate in the regulation of blood pressure. In the present study, we tested the relationship between CGRP and ADMA in spontaneously hypertensive rats (SHRs). For the in vivo study, SHRs were treated with or without L-arginine for 2 weeks, and Wistar Kyoto (WKY) rats were used as controls. Systolic arterial pressure was measured, and the levels of CGRP, ADMA, and NO were analyzed. For the in vitro study, neural cells from dorsal root ganglia were treated with NO inhibitor or donor. Synthesis and release of CGRP were measured. Compared with WKY rats, serum concentration of ADMA in SHRs increased while CGRP and NO level decreased. Treatment with L-arginine significantly decreased blood pressure, concomitantly with an increase in the level of NO and the synthesis and release of CGRP in SHRs, but it did not affect ADMA levels. In cultured neural cells, ADMA reduced the level of NO and inhibited the synthesis and release of CGRP in a concentration-dependent manner. The effects of ADMA were reversed by L-arginine. Treatment with NOC-18, a donor of NO, increased the release and synthesis of CGRP in neural cells in a concentration-dependent manner. Decreased synthesis and release of CGRP is related to a reduction in NO levels, and corresponds to the increased concentrations of ADMA in spontaneously hypertensive rats.
Chen
Qing-Quan
QQ
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Li
Dai
D
Guo
Ren
R
Luo
Dan
D
Yang
Jing
J
Hu
Chang-Ping
CP
Li
Yuan-Jian
YJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009603:Nitroso Compounds / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide