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.
Ikeoka
K
K
Department of Physiology, University of North Carolina, Chapel Hill 27599.
Faber
J E
JE
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D000068438:Brimonidine Tartrate; D006652:Histological Techniques; D066298:In Vitro Techniques; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000804:Angiotensin II; D010656:Phenylephrine; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D011224:Prazosin