人乳内动脉对非肽类血管加压素拮抗剂的反应。

Human internal mammary artery responses to non-peptide vasopressin antagonists.

Liu J J, Phillips P A, Burrell L M, Buxton B B, Johnston C I

Department of Cardiac Surgery, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.

Clin Exp Pharmacol Physiol. 1994 Feb;21(2):121-4. doi: 10.1111/j.1440-1681.1994.tb02478.x.

Abstract

OPC-21268 and OPC-31260 are newly developed orally active non-peptide vasopressin (AVP) V1 and V2 receptor antagonists, respectively. The effects of the two compounds on human vessels have not been studied. 2. The effects of the two compounds on AVP-induced contraction of human internal mammary arteries (IMA) were investigated. Their effects were compared with the peptide V1 and V2 antagonists d(CH2)5Sar7AVP (SAVP) and d(CH2)5D-Ileu2Ileu4AVP (Ileu2Ileu4AVP), respectively. 3. The V1 antagonist OPC-21268 failed to antagonize AVP-induced contraction at low concentrations and potentiated the contraction at higher concentration (3 x 10(-7) mol/L, P < 0.05). It also caused a mild direct contractile effect on IMA. In contrast, the peptide V1 antagonist SAVP potently inhibited the AVP-induced contraction, indicating that functionally constrictor V1 receptors exist in IMA. Both the nonpeptide and peptide V2 antagonists OPC-31260 (3 x 10(-6) mol/L) and Ileu2Ileu4AVP significantly antagonized the AVP-induced contraction (P < 0.01). 4. The AVP-induced contraction was reversed by high concentrations of OPC-31260 (10(-6) mol/L-3 x 10(-5) mol/L) but not by OPC-21268 (up to 3 x 10(-5) mol/L). 5. These studies indicate that, in human IMA, OPC-21268 is a partial V1 receptor agonist with no V1 receptor antagonist activity, while OPC-31260 is a V1 receptor antagonist. The results also indicate that Ileu2Ileu4AVP may be a V1 receptor antagonist in humans.

摘要

OPC - 21268和OPC - 31260分别是新开发的口服活性非肽类血管加压素（AVP）V1和V2受体拮抗剂。这两种化合物对人体血管的作用尚未得到研究。2. 研究了这两种化合物对AVP诱导的人乳内动脉（IMA）收缩的影响。分别将它们的作用与肽类V1和V2拮抗剂d(CH2)5Sar7AVP（SAVP）和d(CH2)5D - Ileu2Ileu4AVP（Ileu2Ileu4AVP）进行比较。3. V1拮抗剂OPC - 21268在低浓度时未能拮抗AVP诱导的收缩，而在较高浓度（3×10(-7) mol/L，P < 0.05）时增强了收缩。它还对IMA产生轻度的直接收缩作用。相比之下，肽类V1拮抗剂SAVP有效抑制了AVP诱导的收缩，表明IMA中存在功能性收缩性V1受体。非肽类和肽类V2拮抗剂OPC - 31260（3×10(-6) mol/L）和Ileu2Ileu4AVP均显著拮抗了AVP诱导的收缩（P < 0.01）。4. 高浓度的OPC - 31260（10(-6) mol/L - 3×10(-5) mol/L）可逆转AVP诱导的收缩，但OPC - 21268（高达3×10(-5) mol/L）则不能。5. 这些研究表明，在人IMA中，OPC - 21268是一种部分V1受体激动剂，不具有V1受体拮抗剂活性，而OPC - 31260是一种V1受体拮抗剂。结果还表明，Ileu2Ileu4AVP在人体内可能是一种V1受体拮抗剂。