Combination of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide activate postnatal vasculogenesis in spontaneously hypertensive rats.
Cardiovascular risk factors are associated with reduction in both the number and function of vascular progenitor cells. We hypothesized that 1) hypertension abrogates postnatal vasculogenesis, and 2) antihypertensive treatment based on the combination of perindopril (angiotensin-converting enzyme inhibitor) and indapamide (diuretic) may counteract hypertension-induced alteration in progenitor cell-related effects. Postischemic neovascularization was significantly lower in untreated spontaneously hypertensive rats (SHRs) compared with Wistar Kyoto (WKY) rats (p < 0.05). Treatment of SHRs with perindopril and the combination of perindopril/indapamide reduced the blood pressure levels and normalized vessel growth in ischemic area. Cotreatment with perindopril and indapamide increased vascular endothelial growth factor and endothelial nitric-oxide synthase protein contents, two key proangiogenic factors. It is interesting to note that 14 days after bone marrow mononuclear cell (BM-MNC) transplantation, revascularization was significantly lower in ischemic SHRs receiving BM-MNCs isolated from SHRs compared with those receiving BM-MNCs isolated from WKY rats (p < 0.05). Alteration in proangiogenic potential of SHR BM-MNCs was probably related to the reduction in their ability to differentiate into endothelial progenitor cells in vitro. Furthermore, the number of circulating endothelial progenitor cells (EPCs) was reduced by 3.1-fold in SHRs compared with WKY rats (p < 0.001). Treatments with perindopril or perindopril/indapamide restored the ability of BM-MNCs to differentiate in vitro into EPCs, increased the number of circulating EPCs, and re-established BM-MNC proangiogenic effects. Therefore, hypertension is associated with a decrease in the number of circulating progenitor cells and in the BM-MNC proangiogenic potential, probably leading to vascular complications in this setting. The combination of perindopril and indapamide counteracts hypertension-induced alterations in progenitor cell-related effects and restores blood vessel growth.
You
Dong
D
Institut National de la Santé et de la Recherche Médicale, Unité 689, Hopital Lariboisière, 41 Blvd. de la Chapelle, 75475 Paris cedex 10, France.
Cochain
Clément
C
Loinard
Céline
C
Vilar
José
J
Mees
Barend
B
Duriez
Micheline
M
Lévy
Bernard I
BI
Silvestre
Jean-Sébastien
JS
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005263:Femoral Artery / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007190:Indapamide / Q000627:therapeutic use*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D020913:Perindopril / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D018952:Antigens, CD34; D000959:Antihypertensive Agents; D004232:Diuretics; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019009:Proto-Oncogene Proteins c-kit; D007190:Indapamide; D020913:Perindopril