Jianping Li1, Donna H Wang. 1. Department of Medicine, Michigan State University, East Lansing, MI 48824, USA.
Abstract
OBJECTIVE: To test the hypothesis that sensory afferents are significant functional components in preventing salt-induced increases in blood pressure. DESIGN AND METHODS: Neonatal Wistar rats were subcutaneously injected with 50 mg/kg capsaicin or vehicle on the first and second days of life. After weaning, male rats were divided into three groups and treated for 4 weeks with: control plus normal (0.5%, CON-NS) or high (4%, CON-HS) sodium diet, and capsaicin pretreatment plus HS diet (CAP-HS). Mean arterial pressure (MAP) and its response to bolus injection of calcitonin gene-related peptide (CGRP) and its antagonist, CGRP(8-37), were measured by carotid arterial catheterization. Radioimmunoassay was used to measure CGRP levels in plasma and dorsal root ganglia (DRG). Expression of components of the CGRP receptor, calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1), was determined by the use of Western blot analysis. RESULTS: Baseline MAP was increased in CAP-HS compared with CON-HS and CON-NS rats, and it was higher in CON-HS than in CON-NS rats. MAP response to exogenous CGRP was enhanced in CAP-HS and CON-HS than in CON-NS rats, but MAP response to CGRP(8-37) was increased only in CON-HS rats. Plasma CGRP levels were not different among three groups, but CGRP content in DRG was decreased in CAP-HS compared with CON-HS and CON-NS rats. CRLR expression in mesenteric resistance arteries was upregulated in CAP-HS and CON-HS compared with CON-NS rats, but RAMP1 content was not different among these groups. CONCLUSION: Chronic high-salt intake upregulates expression of mesenteric CGRP receptors without altering CGRP levels in plasma and DRG. Increased expression of mesenteric CGRP receptors may play a counter regulatory role in attenuating salt-induced increases in blood pressure.
OBJECTIVE: To test the hypothesis that sensory afferents are significant functional components in preventing salt-induced increases in blood pressure. DESIGN AND METHODS: Neonatal Wistar rats were subcutaneously injected with 50 mg/kg capsaicin or vehicle on the first and second days of life. After weaning, male rats were divided into three groups and treated for 4 weeks with: control plus normal (0.5%, CON-NS) or high (4%, CON-HS) sodium diet, and capsaicin pretreatment plus HS diet (CAP-HS). Mean arterial pressure (MAP) and its response to bolus injection of calcitonin gene-related peptide (CGRP) and its antagonist, CGRP(8-37), were measured by carotid arterial catheterization. Radioimmunoassay was used to measure CGRP levels in plasma and dorsal root ganglia (DRG). Expression of components of the CGRP receptor, calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1), was determined by the use of Western blot analysis. RESULTS: Baseline MAP was increased in CAP-HS compared with CON-HS and CON-NS rats, and it was higher in CON-HS than in CON-NS rats. MAP response to exogenous CGRP was enhanced in CAP-HS and CON-HS than in CON-NS rats, but MAP response to CGRP(8-37) was increased only in CON-HS rats. Plasma CGRP levels were not different among three groups, but CGRP content in DRG was decreased in CAP-HS compared with CON-HS and CON-NS rats. CRLR expression in mesenteric resistance arteries was upregulated in CAP-HS and CON-HS compared with CON-NS rats, but RAMP1 content was not different among these groups. CONCLUSION: Chronic high-salt intake upregulates expression of mesenteric CGRP receptors without altering CGRP levels in plasma and DRG. Increased expression of mesenteric CGRP receptors may play a counter regulatory role in attenuating salt-induced increases in blood pressure.