Vicaut E, Montalescot G, Hou X, Stucker O, Teisseire B
Laboratoire de Biophysique, Hopital F. Widal, Paris, France.
Microvasc Res. 1989 Jan;37(1):28-41. doi: 10.1016/0026-2862(89)90070-8.
Several aspects of the differences between the responses of the second- to fifth-order arterioles (A2 to A5) to intraarterial administration of angiotensin II (AII) were studied by intravital microscopy on an original preparation of rat cremaster muscle. Dose-response curves displayed a leftward shift when the arteriolar order increased. Doses inducing 50% vasoconstriction were 15.1, 0.51, and 0.08 micrograms for A3, A4, and A5, respectively. For A2, very small vasoconstriction was found even at the highest dose of angiotensin II. The dynamics of the response were also dependent on the arteriolar order. The duration of the peak of vasoconstriction increased from A3 to A5, and the interval between the contact of vascular wall with drug and the response was smaller in A4 and A5 than in A3. To understand the effect of diameter as a determinant of heterogeneity in the degree of arteriolar vasoconstriction, norepinephrine was administered under the same conditions as angiotensin II, and responses were measured on arterioles with the same morphological characteristics as those examined after angiotensin II. When comparing the regression curves for the percentage of vasoconstriction vs diameter, we found that this relationship was drug dependent. The significantly steeper slope for angiotensin II than for norepinephrine excluded the possibility that heterogeneity of the degree of vasoconstriction is solely due to differences between the morphological characteristics of the arterioles. Since tachyphylaxis to AII is considered to be a reflection of the drug-receptor interaction, we also studied the magnitude of this phenomenon from proximal to distal parts of the arteriolar network. We showed that the degree of partial tachyphylaxis after 1 microgram AII was dependent on the arteriolar order and a decreasing tachyphylaxis gradient was evidenced from A3 to A5 arterioles.
采用活体显微镜技术，在大鼠提睾肌的原始标本上，研究了二级至五级小动脉（A2至A5）对动脉内注射血管紧张素II（AII）反应的几个差异方面。当小动脉级别增加时，剂量-反应曲线向左移动。诱导50%血管收缩的剂量，A3、A4和A5分别为15.1、0.51和0.08微克。对于A2，即使在血管紧张素II的最高剂量下，也仅发现非常小的血管收缩。反应的动力学也取决于小动脉级别。血管收缩峰值的持续时间从A3到A5增加，血管壁与药物接触到反应之间的间隔在A4和A5中比在A3中更小。为了理解直径作为小动脉血管收缩程度异质性决定因素的作用，在与血管紧张素II相同的条件下给予去甲肾上腺素，并在与血管紧张素II检查后具有相同形态特征的小动脉上测量反应。比较血管收缩百分比与直径的回归曲线时，我们发现这种关系取决于药物。血管紧张素II的斜率比去甲肾上腺素明显更陡，排除了血管收缩程度的异质性仅归因于小动脉形态特征差异的可能性。由于对AII的快速耐受性被认为是药物-受体相互作用的一种反映，我们还从小动脉网络的近端到远端研究了这种现象的程度。我们表明，1微克AII后部分快速耐受性的程度取决于小动脉级别，并且从A3到A5小动脉呈现出递减的快速耐受性梯度。
