Qualitatively different response of isolated rabbit aorta to methylene blue administered from intimal and adventitial...

An isolated rabbit aortic preparation, on which administered drugs act selectively from intimal or adventitial surface, was made. Epinephrine (0.1 nM approximately 10 microM) produced concentration-dependent increase of intraluminal pressure, which is due to increase of contraction of the vascular smooth muscle. Sensitivity of contractile response to epinephrine administered from intimal surface was significantly higher than that administered from adventitial surface. The contractile response to epinephrine administered from intimal surface was reduced by removal of the endothelium. Cocaine (100 microM) potentiated the contractile response to epinephrine administered from adventitial surface. Cocaine also potentiated the contractile response to high concentration of epinephrine administered from intimal surface, while the drug reduced the contractile response to low concentration of epinephrine. Methylene blue (100 microM) administered from adventitial surface produced a marked contraction, while methylene blue administered from intimal surface produced a marked relaxation. The relaxing response to methylene blue administered from intimal surface was reduced by the removal of endothelium. Prazosin (1 microM) suppressed the contractile response to methylene blue administered from adventitial surface, indicating that methylene blue released norepinephrine from adrenergic nerve terminals. The contractile response to epinephrine administered from intimal surface was reduced by methylene blue administered from intimal surface. The present study clearly demonstrated variation in mechanical response of isolated rabbit aortic preparation with intimal or adventitial surface of drug entry.