title: Mobilization of putative high-proliferative-potential endothelial colony-forming cells during antihypertensive treatment in patients with essential hypertension.
abstract: Recent studies have shown that in response to vascular damage or ischemia, bone marrow-derived endothelial progenitor cells (EPCs) are recruited into the circulation. To investigate whether antihypertensive treatment has an influence on the number of circulating EPCs, patients with essential hypertension were treated either with the angiotensin receptor antagonist telmisartan, the calcium channel blocker nisoldipine, or their combination for 6 weeks. At baseline and after 3 and 6 weeks of treatment, EPCs were identified and quantified by fluorescence-activated cell sorting (FACS) analysis and by their capacity to generate colony-forming units of the endothelial lineage (CFU-EC) in a methylcellulose-based assay. During treatment, patients in the nisoldipine groups, but not in the telmisartan group, showed a significant mobilization of EPCs, which in part had the capacity to generate large-sized colonies comprising more than 1,000 cells. Moreover, a remarkable correlation between the number of CFU-EC and the number of circulating CD133(+)/CD34(+)/CD146(+) cells was observed, thereby providing strong evidence that cells with this phenotype represent functional EPCs. No correlation was found between the numbers of CFU-EC and the blood pressure levels at any time point during the treatment. Hence, nisoldipine-induced mobilization of EPCs might represent a novel mechanism by which this antihypertensive compound independently of its blood pressure-lowering effect contributes to vasoprotection in patients with essential hypertension.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Clinical Pharmacology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. benndorf@uke.uni-hamburg.de
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Benndorf
authors.forename: Ursula M
authors.initials: UM
authors.lastname: Gehling
authors.forename: Daniel
authors.initials: D
authors.lastname: Appel
authors.forename: Renke
authors.initials: R
authors.lastname: Maas
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Kathleen
authors.initials: K
authors.lastname: Schlagner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Silberhorn
authors.forename: Dieter K
authors.initials: DK
authors.lastname: Hossfeld
authors.forename: Xavier
authors.initials: X
authors.lastname: Rogiers
authors.forename: Rainer
authors.initials: R
authors.lastname: Böger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D001565:Benzoates / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015737:Nisoldipine / Q000627:therapeutic use; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015703:Antigens, CD; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D002121:Calcium Channel Blockers; D015737:Nisoldipine; D000077333:Telmisartan