title: Hypertension impairs postnatal vasculogenesis: role of antihypertensive agents.
abstract: We analyzed the effect of hypertension on postischemic vasculogenesis. Ischemia was induced by right femoral artery ligature in Wistar Kyoto rats (WKY) or spontaneously hypertensive rats (SHR) treated with or without angiotensin-converting enzyme inhibitor (Perindopril, 0.76 mg/kg/d) and angiotensin type 1 receptor blocker (losartan, 30 mg/kg/d). Basal postischemic neovascularization was reduced in SHR compared to WKY (P<0.05, n=8). Treatment with ACE inhibitor or angiotensin type 1 receptor blocker decreased blood pressure levels by 1.4- and 1.3-fold (P<0.001), respectively and restored vessel growth in SHR to WKY levels. Interestingly, 14 days after bone-marrow mononuclear cell (BM-MNC) transfusion, angiographic scores, capillary density, and foot perfusion were decreased by 1.4-, 1.5-, and 1.2-fold, respectively in SHR transfused with BM-MNCs isolated from SHR compared to those receiving BM-MNCs of WKY (P<0.05, n=6). Alteration in BM-MNCs proangiogenic potential was likely related to the reduction in their ability to mobilize into peripheral circulation, as revealed by the 2.9-fold decrease in number of circulating CD34+/CD117+ cells (P<0.001) and to differentiate into cells with endothelial phenotype, as revealed by the 2.1-fold reduction in percentages of DilLDL/BS-1 lectin positive cells (P<0.001). In addition, reactive oxygen species (ROS) levels were increased by 2.2-fold in SHR BM-MNCs compared to WKY BM-MNCs (P<0.01), as assessed by L-012 luminescence. Cotreatment with ACE inhibitor, angiotensin type 1 receptor blocker, or antioxidants (NAC 3 mmol/L, Apocynin 200 micromol/L) reduced ROS levels, improved the number of DilLDL/BS-1 lectin-positive cells by around 1.5-fold, and restored BM-MNCs proangiogenic effects in ischemic hindlimb. In conclusion, alteration in progenitor cell proangiogenic function may participate to the hypertension-induced impairment in postischemic revascularization.
authors.affiliation: Cardiovascular Research Center INSERM U689 Lariboisière, Paris, France.
authors.forename: Dong
authors.initials: D
authors.lastname: You
authors.forename: Clément
authors.initials: C
authors.lastname: Cochain
authors.forename: Céline
authors.initials: C
authors.lastname: Loinard
authors.forename: José
authors.initials: J
authors.lastname: Vilar
authors.forename: Barend
authors.initials: B
authors.lastname: Mees
authors.forename: Micheline
authors.initials: M
authors.lastname: Duriez
authors.forename: Bernard I
authors.initials: BI
authors.lastname: Lévy
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Silvestre
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D008026:Ligation; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D020913:Perindopril / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D000959:Antihypertensive Agents; D006830:Hydralazine; D019808:Losartan; D020913:Perindopril