Park J K, Kim S Z, Kim J U, Kim Y G, Kim S M, Cho K W
Department of Urology, Chonbuk National University Medical School, Keum-Am-Dong-San, Chonju, South Korea.
Int J Impot Res. 2002 Apr;14(2):72-80. doi: 10.1038/sj.ijir.3900824.
The isometric tension measurement and in vitro autoradiography were used in clitoral cavernosum smooth muscle (CSM). Angiotensin ANG III, ANG IV, ANG II and ANG I induced contractions in clitoral CSM strips. ANG III and ANG I- induced contraction was five times less active than ANG II, whereas ANG IV-induced contraction was 1181-fold less potent than ANG II. Contractile responses to ANG III, ANG IV, ANG II and ANG I were significantly inhibited by type 1 ANG II (AT 1) receptor antagonist Dup 753 but not by type 2 ANG II (AT2) receptor antagonist PD 123,319. Pre-treatment with Nomega-nitro-L-arginine methyl ester, nitric oxide (NO) synthase inhibitor accentuated force of contraction induced by ANG III, ANG IV and ANG II. Amastatin, an aminopeptidase inhibitor enhanced ANG III- and ANG IV-induced contractions. Specific binding sites for 125I-ANG II were found in the clitoral CSM. Specific binding of 125I-ANG II was displaced by unlabeled ANG peptides. This study suggests that the contractile responses to all four peptides of the ANG family are mediated via AT1 receptors but not AT2 receptors. Further, the rank order of potency of contraction was as follows, ANG II> ANG I>ANG III>ANG IV. It is also suggested that peptides of the ANG family have a cross-talk with the NO system and aminopeptidase is involved in the modulation of the tone of clitoral CSM by ANG III and ANG IV.
在阴蒂海绵体平滑肌(CSM)中进行了等长张力测量和体外放射自显影。血管紧张素ANG III、ANG IV、ANG II和ANG I可诱导阴蒂CSM条带收缩。ANG III和ANG I诱导的收缩活性比ANG II低5倍,而ANG IV诱导的收缩效力比ANG II低1181倍。1型血管紧张素II(AT1)受体拮抗剂Dup 753可显著抑制对ANG III、ANG IV、ANG II和ANG I的收缩反应,而2型血管紧张素II(AT2)受体拮抗剂PD 123319则无此作用。用一氧化氮(NO)合酶抑制剂Nω-硝基-L-精氨酸甲酯预处理可增强ANG III、ANG IV和ANG II诱导的收缩力。氨肽酶抑制剂抑肽酶可增强ANG III和ANG IV诱导的收缩。在阴蒂CSM中发现了125I-ANG II的特异性结合位点。未标记的ANG肽可取代125I-ANG II的特异性结合。本研究表明,对ANG家族所有四种肽的收缩反应均通过AT1受体介导,而非AT2受体。此外,收缩效力的顺序如下:ANG II>ANG I>ANG III>ANG IV。还表明ANG家族的肽与NO系统存在相互作用,氨肽酶参与ANG III和ANG IV对阴蒂CSM张力的调节。