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四氧嘧啶诱导的糖尿病兔阴蒂海绵体中血管紧张素肽的活性

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

作者信息

Park Jong Kwan, Lee Soon Oak, Cui Wan Shou, Kim Sung Zoo, Koh Gou Young, Cho Kyung Woo

机构信息

Department of Urology, Chonbuk National University Medical School, Keum-Am-Dong-San, Chonju, South Korea.

出版信息

Eur Urol. 2005 Dec;48(6):1042-50. doi: 10.1016/j.eururo.2005.06.017. Epub 2005 Jul 18.

DOI:10.1016/j.eururo.2005.06.017
PMID:16084009
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 +/- 0.4 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.

摘要

目的

评估血管紧张素(ANG)肽在调节糖尿病兔阴蒂海绵体张力及ANG结合亲和力变化中的作用。

材料与方法

对假手术组和糖尿病组的阴蒂海绵体进行等长张力测量和体外放射自显影。

结果

在张力研究中,糖尿病组阴蒂海绵体条对ANG I、ANG II、ANG III和ANG IV的收缩反应增强(糖尿病组的EC50分别为67.6±27.2、4.3±0.4、189.3±37.3、443.2±0.4 nM,假手术组分别为155.2±76.1、38.3±0.1、528.0±75.2、616.9±69.5 nM)。两组中,ANG II的收缩反应均被1型ANG II受体(AT1)拮抗剂显著抑制,而未被2型ANG II受体(AT2)拮抗剂抑制。在存在Dup 753的情况下,ANG II(1 nM)引起的收缩百分比在假手术组中从36.2±4.6%显著降至6.3±2.4%,在糖尿病组中从56.1±7.7%降至6.0±4.8%。糖尿病组阴蒂海绵体对ANG II的结合亲和力增强(解离常数,假手术组为4.9±1.0 nM,糖尿病组为0.9±0.2 nM),对ANG I、ANG III和ANG IV的结合亲和力也增强(抑制常数,假手术组分别为28.6±1.5、398.7±157.2、3966.5±1524.1 nM,糖尿病组分别为20.6±5.7、78.5±23.7、1098.7±195.5 nM,均p<0.05)。糖尿病组阴蒂海绵体组织中AT1和AT2受体对ANG II的敏感性高于假手术组。

结论

这些结果表明,糖尿病组阴蒂海绵体对所有四种ANG肽的收缩反应均增强。糖尿病组阴蒂海绵体收缩性增强可能与ANG肽对ANG II受体的亲和力增加有关。

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