title: Role of calcitonin gene-related peptide in the phenol-induced neurogenic hypertension in rats.
abstract: Previous investigations have demonstrated that capsaicin-sensitive sensory nerves are involved in the development of hypertension in some rat models of hypertension. To determine the role played by calcitonin gene-related peptide (CGRP; the predominant neurotransmitter in capsaicin-sensitive sensory nerves) in a rat model of neurogenic hypertension, in which hypertension was induced by injecting 50 microl of 10% phenol in the lower pole of the left kidney, systolic blood pressure (SBP) was monitored by the tail-cuff method throughout the experiment. Fifteen days after injection of phenol, mean arterial pressure (MAP), concentrations of CGRP in the plasma, the expression of CGRP mRNA in dorsal root ganglia (DRG) and CGRP content in laminae I and II of the spinal cord were measured. SBP was significantly increased 5 days after the intrarenal injection of phenol (164+/-7 mm Hg, p<0.01). At the end of experiment, blood pressure (BP) was significantly elevated in the phenol-injected rats compared with the controls (SBP: 187+/-6 vs. 122+/-4 mm Hg, p<0.01; MAP: 157.56+/-3.02 vs. 103.80+/-2.04 mm Hg, p<0.01). Treatment with capsaicin, which selectively depletes neurotransmitters from the capsaicin-sensitive nerves, failed to enhance the development of hypertensive responses to the intrarenal injection of phenol. Intravenous administration of CGRP(8-37), the specific CGRP receptor antagonist, also failed to increase the already elevated MAP. The expression of CGRP mRNA (both alpha- and beta-CGRP isoforms), the content of CGRP in laminae I and II of the dorsal horn of the spinal cord and the concentration of CGRP in the plasma was decreased in the rats treated with phenol. These results suggest that CGRP does not play a counterregulatory role in the phenol-induced hypertensive rats, and support the hypothesis that reduction of CGRP (alpha and beta isoforms) could contribute to a blood pressure elevation in this setting.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, No. 90 Xiang-Ya Road, Changsha, Hunan 410078, China.
authors.forename: Pan-Yue
authors.initials: PY
authors.lastname: Deng
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Cai
authors.forename: Han-Wu
authors.initials: HW
authors.lastname: Deng
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002211:Capsaicin / Q000008:administration & dosage; D005727:Ganglia, Spinal / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008916:Miotics / Q000008:administration & dosage; D009475:Neurons, Afferent / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage; D019800:Phenol / Q000008:administration & dosage; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D008916:Miotics; D010446:Peptide Fragments; D020033:Protein Isoforms; D012333:RNA, Messenger; C058636:calcitonin gene-related peptide (8-37); D019800:Phenol; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin