Age-related changes in dorsal root ganglia, circulating and vascular calcitonin gene-related peptide (CGRP) concentrations in female rats: effect of female sex steroid hormones.
The aim of the present study is to investigate whether immunoreactive (I) calcitonin gene-related peptide (CGRP) content is decreased in plasma and mesenteric arteries (resistance arteries) in middle-aged rats and if so, whether sex steroid hormones enhance I-CGRP in middle-aged female rats. We also examined whether vascular CGRP receptor components, calcitonin receptor like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1) are elevated by sex steroid hormones treatment in middle-aged female rats. Young adult (3 months old) and middle-aged (10-12 months old) ovariectomized rats were treated subcutaneously with estradiol-17beta (E2; 2 mg), progesterone (P4; 5 mg), E2+P4 (2 mg+20 mg) or placebo (control). Radioimmunoassay and Western blot analysis were performed to measure I-CGRP content and CGRP receptor components in dorsal root ganglia (DRG), in resistance arteries and in plasma. Immunofluorescent staining methods were employed to determine cellular localization of CRLR, RAMP1 in resistance arteries. Our data demonstrated that I-CGRP content was significantly (p<0.05) lower in the plasma and resistance arteries of middle-aged female rats compared to young controls. Both RAMP1 and CRLR were concentrated in vascular endothelium and the underlying smooth muscle cells. RAMP1 but not CRLR appeared to be decreased in middle-aged rat vasculature. Chronic perfusion of sex steroid hormones to ovariectomized rats: 1 significantly (p<0.05) elevated I-CGRP in the DRG and in the plasma, and (2) significantly elevated RAMP1 (p<0.05) but did not alter CRLR in resistance arteries. These data suggest that female sex steroid treatment enhances I-CGRP and its receptors, and thus regulate the blood pressure in aged female rats.
Department of Obstetrics and Gynecology, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, United States. pgangula@mmc.edu
Pandu R R
PR
Gangula
Madhu
M
Chauhan
Luckey
L
Reed
Chandra
C
Yallampalli
D000375:Aging; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000378:metabolism*; D058286:Calcitonin Receptor-Like Protein; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin / Q000378:metabolism
D058286:Calcitonin Receptor-Like Protein; C545580:Calcrl protein, rat; D006728:Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C545508:Ramp1 protein, rat; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin; D011374:Progesterone; D004958:Estradiol; D015740:Calcitonin Gene-Related Peptide