Improvement of Endothelial Function of the Corpus Cavernosum in Apolipoprotein E Knockout Mice Treated with Irbesartan

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 327; no. 3; pp. 692 - 698
• Main Authors: Baumhäkel, Magnus, Custodis, Florian, Schlimmer, Nils, Laufs, Ulrich, Böhm, Michael
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.12.2008
• Subjects: Animals; Aorta; Apolipoproteins E - deficiency; Biphenyl Compounds - pharmacology; Blood Pressure; Endothelium - drug effects; Endothelium - physiology; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Hydralazine - pharmacology; Male; Mice; Mice, Knockout; Nitric Oxide; Oxidative Stress; Penile Erection - drug effects; Penis - cytology; Penis - drug effects; Receptors, Angiotensin; Renin-Angiotensin System; Tetrazoles - pharmacology
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.108.140533

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.