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Long Term Induction of Heme Oxygenase Ameliorates Angiotensin II Dependent Hypertension in Sprague Dawley Rats Transduced with HO1‐Lentiviral Construct
Author(s) -
puri nitin,
vanella luca,
sodhi komal,
cao Jian,
Kim Dong Hyun,
Inoue Kazuyoshi,
quilley John,
abraham nader g
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.661.4
Subject(s) - enos , medicine , endocrinology , creatinine , heme oxygenase , endothelial dysfunction , endothelium , angiotensin ii , renal function , chemistry , blood pressure , nitric oxide synthase , heme , nitric oxide , enzyme , biochemistry
This study examines the long term effects of endothelium targeting human lentiviral‐HO1 construct on reno‐vascular dysfunction caused by ANG II in SD rats. Vascular endothelium was transduced with HO1‐lentiviral construct under the control of endothelium specific promoters‐ VE‐Cadherin (VECAD‐HO‐1) via a bolus injection of VECAD‐HO‐1 into the renal artery, resulting in induction of human HO‐1 for up to 6–9 weeks. SD rats implanted with ANG II mini pumps were treated with either lentivirus carrying the HO‐1 or GFP insert. Infusion of ANG II increased blood pressure (BP) (p<0.001), inhibited endothelial function, reduced p‐eNOS/eNOS levels along with attenuation of renal and plasma levels of adiponectin (p<0.05). Renal and vascular iNOS expression was enhanced accompanied by renal damage, as evidenced by increased urinary proteins and serum creatinine levels (p<0.05). HO‐1 transduction via VECAD‐HO‐1 construct attenuated the increase in BP (p<0.05), improved vascular function, increased p‐eNOS expression, increased plasma adiponectin (p<0.05), and prevented the elevation in urinary proteins and plasma creatinine in ANG II‐treated rats. Collectively, these findings demonstrate that an endothelial‐specific increase in HO‐1 expression attenuates ANG II hypertension and the associated reno‐vascular dysfunction via restoration of endothelial function and increase in serum adiponectin.