Protective effects of grape seed proanthocyanidins on cardiovascular remodeling in DOCA-salt hypertension rats.
Cardiovascular remodeling, as a hallmark of hypertension-induced pathophysiology, causes substantial cardiovascular morbidity and mortality. There is increasing evidence that has demonstrated a broad spectrum of pharmacological and therapeutic benefits of grape seed proanthocyanidins (GSP) against oxidative stress and cardiovascular diseases. In this study, 180- to 200-g SD rats treated with DOCA (120 mg/week sc with 1% NaCl and 0.2% KCl in drinking water) and GSP (150, 240, 384 mg/kg) or amlodipine (ALM) (5 mg/kg) for 4 weeks were recruited. The protective effects of GSP on blood pressure and cardiovascular remodeling in rats with DOCA-salt-induced hypertension were investigated. Our results indicated that DOCA-salt could induce hypertension, cardiovascular remodeling and dysfunction, oxidative stress and the release of endothelin-1 (ET-1) and could increase JNK1/2 and p38MAPK phosphorylation. GSP or ALM treatments significantly improved hypertension, cardiovascular remodeling and dysfunction and oxidative stress, restrained the release of ET-1 and down-regulated the JNK1/2 and p38MAPK phosphorylation. These findings demonstrate that GSP has protective effects against increase of blood pressure induced by DOCA-salt hypertension and cardiovascular remodeling by inhibiting the reactive oxygen species/mitogen-activated protein kinase pathway via restraining the release of ET-1.
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China; Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
Ling-ling
LL
Huang
Department of Clinical Pharmacy, Lishui People's Hospital, Zhejiang 323000, China.
Chen
C
Pan
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China.
Li
L
Wang
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China.
Ling
L
Ding
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China.
Kun
K
Guo
Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
Hong-zhi
HZ
Wang
Department of General Surgery, the Fourth Affiliated Hospital, Anhui Medical University, Hefei 230032, China. Electronic address: xuaman166@sina.com.
A-Man
AM
Xu
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China. Electronic address: aydgs@126.com.
Shan
S
Gao
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism; D064791:Desoxycorticosterone Acetate / Q000008:administration & dosage / Q000009:adverse effects*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D056604:Grape Seed Extract / Q000494:pharmacology*; D006909:Hydroxyproline / Q000097:blood; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D019332:Endothelin-1; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; D008315:Malondialdehyde; D064791:Desoxycorticosterone Acetate; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; D006909:Hydroxyproline
Antioxidant; Cardiovascular remodeling; DOCA-salt hypertension; Grape seed proanthocyanidins; JNK; p38