Arteriolar vasoconstriction and tachyphylaxis with intraarterial angiotensin II.
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.