Activity of Angiotensin Peptides in Clitoral Cavernosum of Alloxan Induced Diabetic Rabbit

Abstract Objectives To assess the role of peptides of the angiotensin (ANG) on the regulation of clitoral cavernosum tone and changes in ANG binding affinity in the rabbit with diabetes mellitus. Material and methods The isometric tension measurement and in vitro autoradiography were used in sham and diabetic clitoral cavernosum. Results In tension study, contractility in response to ANG I, ANG II, ANG III and ANG IV was enhanced in diabetic clitoral cavernosum strips (EC50 was 67.6±27.2, 4.3±0.4, 189.3±37.3, 443.2±0.4nM for diabetic versus 155.2±76.1, 38.3±0.1, 528.0±75.2, 616.9±69.5nM for sham, respectively). Contractile responses to ANG II was significantly inhibited by type 1 ANG II receptor (AT1) antagonist but not by type 2 ANG II receptor (AT2) antagonist in both groups. Percentages in contractions by ANG II (1nM) in the presence of Dup 753 decreased significantly 36.2±4.6 to 6.3±2.4% in sham and 56.1±7.7 to 6.0±4.8% in diabetic group. The binding affinities were enhanced in diabetic clitoral cavernosum for ANG II (dissociation constant, 4.9±1.0 for sham versus 0.9±0.2nM for diabetic) and for ANG I, ANG III, and ANG IV (inhibitory constant, 28.6±1.5, 398.7±157.2, and 3966.5±1524.1nM for sham versus 20.6±5.7, 78.5±23.7, and 1098.7±195.5nM, for diabetic, respectively, all p Conclusions This results suggest that the contractile responses to all four ANG peptides are enhanced in the diabetic clitoral cavernosum. Enhancement of contractility in diabetic clitoral cavernosum may be related to the increased affinity to ANG II receptors for ANG peptides.