Abstract
Angiotensin receptor blockers enhance endothelial function and are suggested to improve erectile function. The effects and underlying mechanisms of treatment with the angiotensin receptor blocker irbesartan on penile endothelial function in apolipoprotein E (ApoE)-/- mice were determined. Wild-type (C57/B6) and ApoE-/- mice were fed with a high-fat, cholesterol-rich diet for 7 weeks and treated with irbesartan (50 mg/kg · day) or hydralazine (250 mg/l). Vital parameters were measured with the tail-cuff method. Endothelial (aortic rings) and erectile function (corpora cavernosa) were assessed by pharmacological stimulation in an organ bath chamber. Oxidative stress and angiotensin receptor expression were determined. Blood pressure was significantly decreased in irbesartan- and hydralazine-treated ApoE-/- mice (p < 0.05) compared with controls and wild-type mice. Endothelial function of the aorta and corpus cavernosum was significantly impaired in ApoE-/- mice (p < 0.05) and could be restored by treatment with irbesartan (p < 0.05). Consistently, nitric oxide production of corpora cavernosa was impaired in ApoE-/- mice (p < 0.01), with a restoration in irbesartan- but not hydralazine-treated mice. Dihydroethidium-stained sections and lipid peroxidase assay revealed a reduction of superoxide production in irbesartan (p < 0.05) compared with hydralazine-treated and control ApoE-/- mice. In summary, irbesartan improves penile endothelial function in ApoE-/- mice by reduction of vascular and cavernosal oxidative stress. This result emphasizes the beneficial effect of inhibition of the renin-angiotensin system even in terms of erectile function.
Footnotes
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Animal studies were supported by grants by Homburger Forschungsförderungsprogramm (Germany) and Bristol-Myers Squibb (Munich, Germany). M.Bö. and U.L. are supported by the Deutsche Forschungsgemeinschaft (KFO 196). M.Ba. and M.Bö. received grants for clinical trials and animal studies from Bristol-Myers Squibb (Germany) not related to the present study.
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M.Ba. and F.C. contributed equally to this work.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.108.140533.
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ABBREVIATIONS: ED, erectile dysfunction; ApoE, apolipoprotein E; LDL, low-density lipoprotein; AoR, aortic ring(s); CCS, corpora cavernosal strip(s); DHE, dihydroethidium; DAF, diaminofluorescein; WT, wild-type; ROS, reactive oxygen species.
- Received April 29, 2008.
- Accepted September 22, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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