Combination of the Angiotensin-Converting Enzyme Inhibitor Perindopril and the Diuretic Indapamide Activate Postnatal Vasculogenesis in Spontaneously Hypertensive Rats

Autor: Clément Cochain, Dong You, Micheline Duriez, Jean-Sébastien Silvestre, Jose Manuel Vilar, Céline Loinard, Barend Mees, Bernard I. Levy
Rok vydání: 2008
Předmět:
Male
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Nitric Oxide Synthase Type III
Neovascularization
Physiologic
Nitric Oxide Synthase Type II
Angiotensin-Converting Enzyme Inhibitors
Antigens
CD34
Pharmacology
Rats
Inbred WKY
chemistry.chemical_compound
Vasculogenesis
Rats
Inbred SHR
Internal medicine
medicine
Perindopril
Animals
Progenitor cell
Diuretics
Muscle
Skeletal
Antihypertensive Agents
biology
business.industry
Indapamide
Angiotensin-converting enzyme
Hematopoietic Stem Cells
Rats
Femoral Artery
Vascular endothelial growth factor
Transplantation
Proto-Oncogene Proteins c-kit
medicine.anatomical_structure
Endocrinology
chemistry
Hypertension
biology.protein
Molecular Medicine
Drug Therapy
Combination
business
circulatory and respiratory physiology
Blood vessel
medicine.drug
Zdroj: Journal of Pharmacology and Experimental Therapeutics. 325:766-773
ISSN: 1521-0103
0022-3565
DOI: 10.1124/jpet.107.131532
Popis: 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.
Databáze: OpenAIRE
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