Effects of ACE inhibition and beta-blockade on female genital structures in spontaneously hypertensive rats.
OBJECTIVE
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).


METHODS
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-alpha-smooth muscle actin (alpha-SMA), anti-collagen I and III, anti-transforming growth factor beta(1) (TGFbeta(1)), 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, alpha-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. TGFbeta(1) 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 TGFbeta(1) 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.


CONCLUSIONS
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
Jorge E
JE
Laboratory of Experimental Medicine, Hospital Alemán, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. jtoblli@hospitalaleman.com
Cao
Gabriel
G
Casabé
Adolfo R
AR
Bechara
Amado J
AJ
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002987:Clitoris / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006973:Hypertension / Q000188:drug therapy*; D007150:Immunohistochemistry / Q000379:methods; D051381:Rats; D011921:Rats, Inbred WKY
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D003094:Collagen