Renin angiotensin system in rabbit corpus cavernosum: Functional characterization of angiotensin II receptors

Purpose: The regulation of the corporal smooth muscle tone is important in the process of penile erection. Although specific angiotensin (ANG) II binding to and effects of ANG II on some reproductive structures have been studied, the presence of the renin-angiotensin system has not yet been defined in the corpus cavernosum. ANG II is formed from ANG I by angiotensin I-converting enzyme (ACE). ANG II and ANG I produce contractions in vascular smooth muscles. Two subtypes of ANG II receptors (AT1 and AT2) have been characterized, The purpose of the present experiments was to determine whether the renin-angiotensin system regulates rabbit corpus cavernosum smooth muscle tone. Materials and Methods: A strip of rabbit corpus cavernosum was mounted in an organ chamber to measure the isometric tension. The specific binding for I-125-ANG II was characterized by in vitro autoradiography. Results: ANG II and ANG I, precursor of ANG II, contracted corpus cavernosum smooth muscle dose-dependently, but the response of smooth muscle to ANG I was 10-fold less than that to ANG II, Contractile responses of smooth muscle to ANG II and ANG I were blocked by Dup 753, a specific inhibitor of ANG II type 1 receptor, but not by PD 123,319, a specific inhibitor of ANG II type 2 receptor. The effect of ANG I was attenuated by captopril, an inhibitor of ACE. Specific binding sites for I-125-ANG II were found in the corpus cavernosum. The dissociation constant (K-d) was 5.32 +/- 1.65 nM, and maximum binding capacity (B-max) was 305.72 +/- 85.24 amol/mm.(2) Specific binding of I-125-ANG II was displaced by Dup 753 (10(-6) M) but not by PD 123,319 (10(-5) M). The inhibitory constant (K-i) for Dup 753 was 8.09 +/- 2.51 nM. Conclusion: The present results suggest that the renin-angiotensin system is involved in the regulation of corpus cavernosum smooth muscle tone bf rabbit and the ANG II receptor subtype AT1 is important in the regulation of penile erection.