Activity of angiotensin peptides in clitoral cavernosum of alloxan induced diabetic rabbit.
OBJECTIVE
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.


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 +/- 0.4 nM for diabetic versus 155.2 +/- 76.1, 38.3 +/- 0.1, 528.0 +/- 75.2, 616.9 +/- 69.5 nM 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 (1 nM) 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 +/- 0.2 nM for diabetic) and for ANG I, ANG III, and ANG IV (inhibitory constant, 28.6 +/- 1.5, 398.7 +/- 157.2, and 3966.5 +/- 1524.1 nM for sham versus 20.6 +/- 5.7, 78.5 +/- 23.7, and 1098.7 +/- 195.5 nM, for diabetic, respectively, all p < 0.05). Sensitivities of AT1 and AT2 receptors to ANG II enhanced in diabetic than sham clitoral cavernosum tissue.


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.
Park
Jong Kwan
JK
Department of Urology, Chonbuk National University Medical School, Keum-Am-Dong-San, Chonju, South Korea. rain@chonbuk.ac.kr
Lee
Soon Oak
SO
Cui
Wan Shou
WS
Kim
Sung Zoo
SZ
Koh
Gou Young
GY
Cho
Kyung Woo
KW
D000496:Alloxan; D000809:Angiotensins / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002987:Clitoris / Q000187:drug effects* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D012016:Reference Values; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques
D000809:Angiotensins; D000496:Alloxan