title: Effect of olmesartan medoxomil on number and survival of circulating endothelial progenitor cells and calcitonin gene related peptide in hypertensive patients.
abstract: OBJECTIVE
  Injury of vascular endothelium, crucial in vascular disease, is repaired via circulating endothelial progenitor cells (cEPCs). In hypertension, cEPCs number is reduced and function impaired adding further risk for cardiovascular (CV) events. Angiotensin II (Ang II)-induced oxidative stress (OxSt), accelerates cEPCs senescence. Calcitonin gene-related peptide (CGRP), able to prevent and reverse Ang II-induced cEPCs senescence, is reduced in hypertension and stimulated by the antioxidant and anti-inflammatory heme oxygenase (HO)-1. In essential hypertensive patients olmesartan reduced OxSt and markers of CV remodeling and increased HO-1. This study reports in essential hypertensive patients the effect of 6 months treatment with olmesartan on plasma level of CGRP and number and survival of cEPCs.
  
  
  RESULTS
  In 20 essential hypertensive patients treated with olmesartan medoxomil (20  mg per day for 6 months), cEPCs (CD34(+)KDR(+), CD133(+)KDR(+) and CD34(+)CD133(+)KDR(+)) (direct 3-color flow cytometry analysis), apoptosis of cEPCs (CD133(+)KDR(+) cells with Annexin V expression), CGRP determination (ELISA) and HO-1 protein level (western blot) were assessed at baseline and after 3 and 6 months of treatments. Olmesartan normalized blood pressure (P < 0.001), increased cEPCs from baseline (CD34(+)KDR(+): P < 0.003; CD133(+)KDR(+): P < 0.0002; CD34(+)CD133(+)KDR(+): P = 0.0008), reduced cEPCs apoptosis (P < 0.001) and increased CGRP (P < 0.013) and HO-1 (P = 0.039).
  
  
  CONCLUSIONS
  These results provide a mechanistic rationale for the olmesartan's antioxidant and anti-inflammatory potential translation toward antiatherosclerotic and antiremodeling effects reported on clinical ground.
authors.affiliation: aDepartment of Medicine, Clinica Medica 4 bEmathology and Immunology, University of Padova, Italy.
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Calò
authors.forename: Lucia
authors.initials: L
authors.lastname: Dal Maso
authors.forename: Elisa
authors.initials: E
authors.lastname: Pagnin
authors.forename: Verdiana
authors.initials: V
authors.lastname: Ravarotto
authors.forename: Monica
authors.initials: M
authors.lastname: Facco
authors.forename: Elisa
authors.initials: E
authors.lastname: Boscaro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maiolino
authors.forename: Achille C
authors.initials: AC
authors.lastname: Pessina
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Rossi
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000097:blood*; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D051547:Heme Oxygenase-1 / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D000068557:Olmesartan Medoxomil; D013234:Stem Cells / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; D051547:Heme Oxygenase-1; D015740:Calcitonin Gene-Related Peptide