Vasculoprotective effect of cilostazol in aldosterone-induced hypertensive rats.
Cilostazol (CILO), a selective inhibitor of phosphodiesterase 3 with potent antithrombotic property, has been shown to have a vasculoprotective effect in atherosclerosis animal models due to its potential anti-inflammatory and antioxidant actions. This study was undertaken to investigate whether CILO has in fact any vasculoprotective effects in aldosterone-induced hypertensive rats (Aldo-rats), and whether CILO affects Aldo-induced oxidative stress, nitric oxide (NO) production and pro-inflammatory gene expression. Treatment with CILO markedly ameliorated perivascular inflammatory changes in the coronary arterioles of Aldo-rats without affecting the systolic blood pressure and left ventricular weight. Treatment with CILO also prevented the increase in plasma levels of thiobarbituric acid-reactive substances, an oxidative stress marker, as well as decreased urinary NOx excretion in Aldo-rats. Furthermore, CILO almost completely inhibited a set of upregulated proinflammatory genes (ICAM-1, MCP-1, PDGF-A, osteopontin, MMP-2 and ACE), as well as NAD(P)H oxidase components (p22phox, gp91phox, p47phox) and Aldo-inducible genes (SGK-1 and NHE-1) in the aortic tissues from Aldo-rats. Taken together, this study showed for the first time that CILO prevented Aldo-induced vascular inflammation and injury without affecting the blood pressure, suggesting its vasculoprotective effect on Aldo-induced vascular injury independent of blood pressure.
Sakurada
Maya
M
Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Bunkyo-ku, Tokyo, Japan.
Yoshimoto
Takanobu
T
Sekizawa
Naoko
N
Hirono
Yuki
Y
Suzuki
Noriko
N
Hirata
Yukio
Y
D000450:Aldosterone / Q000009:adverse effects*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018932:Chemokine CCL2 / Q000378:metabolism; D000077407:Cilostazol; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D018932:Chemokine CCL2; D000077407:Cilostazol; D017874:Immediate-Early Proteins; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D010726:Phosphodiesterase Inhibitors; D010982:Platelet-Derived Growth Factor; D017346:Protein Serine-Threonine Kinases; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013777:Tetrazoles; D017392:Thiobarbituric Acid Reactive Substances; D000099184:Serum-Glucocorticoid Regulated Kinases; C111835:CCL2 protein, human; C452850:Slc9a1 protein, rat; C075278:platelet-derived growth factor A