ANG II reverses selective inhibition of alpha 2-adrenoceptor sensitivity after in vitro isolation of arterioles.

To determine whether in vitro isolation attenuates alpha 2-reactivity, we examined postjunctional alpha-adrenoceptor sensitivity of isolated rat skeletal muscle first-order arterioles that we have previously characterized in vivo. Microdissected, pressurized arterioles (mean lumen diam +/- SE, 115 +/- 7 microns) were studied after cannulation with micropipettes. As expected, the alpha 1-antagonist, prazosin (10(-8) M), produced a parallel, 10-fold dextral displacement of the phenylephrine (alpha 1-agonist) concentration-response curve, whereas the alpha 2-antagonist, rauwolscine (10(-7) M) had no effect. However, prazosin inhibited UK-14,304 (full alpha 2- but partial alpha 1-agonist), which was opposite to our previous in vivo studies of these vessels; namely, prazosin shifted the UK-14,304 response curve by 21-fold, whereas rauwolscine induced only a twofold shift. These data suggest a loss of alpha 2-adrenoceptor responsiveness after in vitro isolation. In a second experiment, the presence of 10 pM angiotensin II, which was subthreshold for constriction, increased phenylephrine sensitivity 10-fold, UK-14,304 sensitivity 16-fold, and the UK-14,304 maximal response by 63%; the half maximum effective concentration response to UK-14,304 was now abolished by rauwolscine at a concentration that did not inhibit phenylephrine constriction. These data suggest that in vitro conditions selectively attenuate alpha 2-adrenoceptor sensitivity, and that subthreshold angiotensin II restores alpha 2-sensitivity to in vivo values.