Facilitating interaction between rauwolscine and angiotensin in the mesenteric artery of the rabbit

The interaction between rauwolscine and angiotensin II was investigated in the isolated mesenteric artery of the rabbit. Rauwolscine, known as an antagonist at alpha 2-adrenoceptors, did not induce contraction itself but interacted with angiotensin to produce a facilitated response of the vascular tissue. In the presence of rauwolscine, the contractile response of the tissue to angiotensin was markedly enhanced. The degree of facilitation appeared to be dependent on the rauwolscine concentration used rather than that of angiotensin. Moreover, rauwolscine induced a concentration-dependent increase in tension (pD2 = 6.8) in the presence of even subcontractile concentrations of angiotensin (10(-10) mol/l). This effect was not attributable to an indirect action involving presynaptic catecholamines, as revealed by the use of tissue strips from animals pretreated with reserpine or after chemical sympathectomy. Furthermore, an interaction via the prostaglandin system was excluded by negative results obtained with indomethacin. The 'agonistic effect' of rauwolscine was significantly attenuated by phentolamine (alpha 1/alpha 2) but not by prazosin (alpha 1) or phenoxybenzamine when applied for only a short time. The alpha 2-antagonist BDF 6143 behaved like rauwolscine whereas the alpha 1-antagonist corynanthine, a stereoisomer of rauwolscine, did not. The results indicate that the 'rauwolscine effect' is mediated by a receptor with alpha 2-characteristics. In general, angiotensin appears to interfere with some process which determines the expression of a drug's intrinsic effect.