RENIN ANGIOTENSIN SYSTEM OF RABBIT CLITORAL CAVERNOSUM: INTERACTION WITH NITRIC OXIDE

Abstract

Angiotensin (ANG) II has been known to be a potent modulator for the maintenance of smooth muscle tone of the penile cavernosum. However, its role in clitoral cavernosum is unknown. The clitoris is the homologue of the penis arising from the embryological genital tubercle. We investigated the presence of ANG II receptors, the function of ANG II, and its interaction with nitric oxide (NO) in rabbit clitoral cavernosum. The isometric tension was measured in the strips of clitoral cavernosum. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate expression of AT1a and AT1b ANG II receptor subtype mRNAs. In vitro autoradiography was used to localize ANG II receptors in the clitoral cavernosum. The clitoral cavernosum was contracted dose-dependently by the addition of ANG II. Dup 753 (ANG II type 1 receptor antagonist) inhibited significantly ANG II induced contraction. PD 123,319 (ANG II type 2 receptor antagonist) did not affect the ANG II response. Pretreatment with NG-nitro-L-arginine methyl ester (NO synthase inhibitor) accentuated contractions induced by ANG II. Specific binding sites for 125I-ANG II were found in the clitoral cavernosum. The dissociation constant (Kd) was 0.58 + or - 0.05 nM. Specific binding of 125I-ANG II was displaced by Dup 753 (10-5 M) but not by PD 123,319 (10-5 M). The inhibitory constant (Ki) for Dup 753 was 23. 4 + or - 9.73 nM and mRNAs for AT1a and AT1b receptor subtypes were detected by RT-PCR. The present study shows that ANG II is involved in the regulation of clitoral cavernosum smooth muscle tone via ANG II receptor subtype AT1, and that ANG II has cross-talk with NO.