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Alterations in Endothelial Nitric Oxide Synthase and RhoA/ROCK are Associated with Erectile Dysfunction in Angiotensin II‐induced Hypertensive Rats
Author(s) -
Jin Liming,
Lagoda Gwen A,
Webb R. Clinton,
Burnett Arthur L
Publication year - 2006
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.20.5.a1241-a
Subject(s) - erectile dysfunction , rhoa , endothelial nitric oxide synthase , nitric oxide , nitric oxide synthase , angiotensin ii , atp synthase , renin–angiotensin system , medicine , endocrinology , chemistry , pharmacology , biochemistry , blood pressure , enzyme , signal transduction , enos
Hypertension is strongly associated with erectile dysfunction (ED). The molecular mechanisms causing ED in angiotensin (ANG) II‐induced hypertensive rats have not been investigated. RhoA/ROCK has been shown to maintain corporal smooth muscle contraction through inhibition of the myosin light chain phosphatase target subunit (MYPT1), while endothelial nitric oxide synthase (eNOS) is involved in inducing erection. We hypothesized that decreased eNOS and elevated RhoA/ROCK activity contribute to ED in ANG II‐induced hypertensive rats. Sprague‐Dawley rats were treated with saline or ANG II (60 ng/min/kg) via osmotic pumps. After 28 days, the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) were measured upon cavernous nerve stimulation. Phosphorylation of MYPT1 and protein expressions of RhoA, ROCK I and II and MYPT1 were determined by Western blot analysis. Erectile function which is represented by ICP/MAP was impaired in ANG II‐treated rats (0.23 ± 0.02, 0.25 ± 0.01, 0.32 ± 0.05, 0.38 ± 0.08, and 0.35 ± 0.07 at 1, 2, 3, 4, and 5 volt) compared to control rats (0.43 ± 0.16, 0.54 ± 0.15, 0.60 ± 0.14, 0.69 ± 0.11, and 0.72 ± 0.11, n=4). Total area under the ICP curve was also reduced in ANG II‐treated rats. RhoA protein expression and MYPT‐1 phosphorylation were markedly increased by 28 ± 5% and 43 ± 7% in ANGII‐treated rats, respectively; whereas eNOS protein was significantly reduced by 35 ± 2%. There was no difference in MYPT1 and ROCK isoforms protein expressions. In conclusion, these data suggest that up‐regulation of RhoA/ROCK and down‐regulation of eNOS is associated with ED in ANG II‐induced hypertensive rats.