Different responses to angiotensin-(1-7) in young, aged and diabetic rabbit corpus cavernosum

Abstract

We evaluated the ability of angiotensin-(1-7) [Ang-(1-7)] to produce relaxation of the corpus cavernosum of New Zealand White rabbits. The reactivity of corpus cavernosal strips isolated from young rabbits (8-10 months old) was assessed in organ-bath chambers. Cumulative concentration response curves for Ang-(1-7), angiotensin II (Ang II), carbachol and sodium nitroprusside (SNP) were established. Ang-(1-7) (10(-12) to 10(-5)M) produced a concentration-dependent relaxation of the corpus cavernosal strips with a pD(2) value of 9.8+/-0.3. Ang-(1-7)-induced maximal relaxant response was reduced by 48+/-2%, 57+/-3% and 76+/-2% in the presence of A-779 (10(-6)M), a selective Ang-(1-7) receptor (AT(1-7)) antagonist, nitro-l-arginine methyl ester (l-NAME) (10(-4)M), an inhibitor of nitric oxide (NO) synthase, or iberiotoxin (5 x 10(-8)M), an inhibitor of calcium-activated potassium (BK) channels, respectively. In contrast, Ang II-induced contraction was increased in the presence of A-779. Carbachol-, SNP- and Ang-(1-7)-induced relaxations were significantly reduced whereas Ang-II induced contraction was significantly increased in the cavernosum strips from older (18-24 months old) and diabetic rabbits compared to the young. Pre-incubation of the cavernosum strips obtained from young, older or diabetic rabbits with Ang-(1-7) resulted in a significant attenuation of Ang II-induced contraction. In conclusion, these results demonstrate that Ang-(1-7) can produce nitric oxide-dependent relaxation of the corpus cavernosum through activation of AT(1-7) and BK channels. Older and diabetic animals showed impaired Ang-(1-7)-mediated relaxation suggesting that aging and diabetes related erectile dysfunction (ED) may be partly due to decreased Ang-(1-7)-mediated relaxation of the corpus cavernosum. Acute pre-incubation with Ang-(1-7) was effective in attenuating Ang II-induced contraction of rabbit corpus cavernosum suggesting that the possible role of Ang-(1-7) in treatment of ED should be investigated.