Renin angiotensin system of rabbit clitoral cavernosum: Interaction with nitric oxide

Purpose: Angiotensin (ANG) II has been known to be a potent modulator for t he maintenance of smooth muscle tone of the penile cavernosum. However, its role in clitoral cavernosum is unknown. The clitoris is the homologue of t he penis arising from the embryological genital tubercle. We investigated t he presence of ANG II receptors, the function of ANG II, and its interactio n with nitric oxide (NO) in rabbit clitoral cavernosum. Materials and Methods: The isometric tension was measured in the strips of clitoral cavernosum. Reverse transcriptase polymerase chain reaction (RT-PC R) 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 t he clitoral cavernosum. Results: The clitoral cavernosum was contracted dose-dependently by the add ition of ANG II. Dup 753 (ANG II type 1 receptor antagonist) inhibited sign ificantly ANG II induced contraction. PD 123,319 (ANG II type 2 receptor an tagonist) did not affect the ANG II response. Pretreatment with N-G-nitro-L -arginine methyl ester (NO synthase inhibitor) accentuated contractions ind uced by ANG II. Specific binding sites for I-125-ANG II were found in the c litoral cavernosum, The dissociation constant (K-d) was 0.58 +/- 0.05 nM. S pecific binding of I-125-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 +/- 9.73 nM and mRNAs for AT1a and AT1b receptor subtypes were detected by RT-PCR. Conclusion: The present study shows that ANG II is involved in the regulati on of clitoral cavernosum smooth muscle tone via ANG II receptor subtype AT 1, and that ANG II has cross-talk with NO.