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ORIGINAL RESEARCH—BASIC SCIENCE: Effects of ACE Inhibition and Beta-Blockade on Female Genital Structures in Spontaneously Hypertensive Rats


Jorge E. Toblli, MD, PhD, Laboratory of Experimental Medicine, Hospital Alemán, Av. Pueyrredon 1640, Buenos Aires 1118, Argentina. Tel: 54-11-4827-7000; Fax: 54-11-4805-6087; E-mail:


Introduction and Aim.  This study evaluated the possible differences between an angiotensin converting enzyme (ACE) inhibitor and a beta-blocker concerning their potential protective role on female external genitalia in spontaneously hypertensive rats (SHR).

Main Outcome Measures.  Morphological changes in the clitoris after antihypertensive treatments.

Methods.  For 6 months, SHR received no treatment; SHR + ramipril (RAM), SHR + atenolol (AT), and control Wistar Kyoto (WKY) rats received no treatment. Clitorises were processed for immunohistochemistry using anti-α-smooth muscle actin (α-SMA), anti-collagen I and III, anti-transforming growth factor β1 (TGFβ1), and anti-endothelial nitric oxide synthase (eNOS) antibodies.

Results.  SHR + RAM and SHR + AT presented significantly lower blood pressure in both groups vs. untreated SHR. Compared with WKY, α-SMA was increased in the arteries and in the cavernous spaces of the clitoris together with a marked increase in wall/lumen ratio in clitoral vessels in untreated SHR. All these alterations were diminished in SHR + AT (P < 0.01). SHR + RAM presented differences with respect to SHR + AT in the reduction of these variables. TGFβ1 expression in the vessel wall from the clitoris and collagen I and III deposition in the interstitium from the clitoris in untreated SHR were significantly more (P < 0.01) than in WKY. While SHR + AT showed a mild decrease in these variables, SHR + RAM presented a significant reduction (P < 0.01) in TGFβ1 expression interstitial fibrosis and in both types of collagens. Positive immunostaining of eNOS in the sinusoidal endothelium from the clitoris was less (P < 0.01) in untreated SHR (3.4 ± 1.3%) and SHR + AT (5.1 ± 1.2%) than in SHR + RAM (17.2 ± 1.6%) and WKY (15.9 ± 1.7%). Untreated SHR and SHR + AT presented more surrounding connective tissue at the perineurium in the clitoris (P < 0.01) than SHR + RAM.

Conclusion.  ACE inhibition provided a considerable protective role on the female external genitalia structures in SHR by a mechanism that may be, at least in part, independent of the degree of blood pressure lowering. Toblli JE, Cao G, Casabé AR, and Bechara AJ. Effects of ACE inhibition and beta-blockade on female genital structures in spontaneously hypertensive rats. J Sex Med 2007;4:1593–1603.