Myotropic actions of angiotensin and noradrenaline in strips of rabbit aortae

Abstract
The myotropic effects of angiotensin II (ATII), some analogues and fragments of ATII, and noradrenaline (NA) have been studied in rabbit aorta strips, in vitro. Contractions elicited by NA consist of an initial rapid and of a slow late phase, while ATII produces a slow and gradual increase of tension, especially at low concentrations. A good correlation has been shown to exist between the time required to increase tension by 50% and the concentration of ATII or the pD2 values of various angiotensins. These results suggest that the pattern of the contractions produced by NA and ATII is influenced by the different diffusion rates of the two agents. Aortic strips contracted by NA maintain a stable plateau of contraction for more than 20 min, while tension in those stimulated by maximal concentrations of ATII fades. This fade persists in the presence of indomethacin, of high concentrations of extracellular Ca2+, and does not depend on the metabolism of the peptide.Extracellular Ca2+ plays an important role in the stimulation or rabbit aorta strips by ATII and NA, but does not effect the binding of ATII to its specific receptors over a wide range of concentrations, and reduces slightly the binding of NA. The ratio of maximum response (ATII–NA) is influenced by external Ca2+ and corresponds to 0.54 in the presence of low Ca2+ (0.01 mM), and to 0.86 in the presence of 2.5 mM Ca2+. Both agonists maintain a fraction of their myotropic effect in tissues exposed to Ca2+-free medium for short periods (10−20 min) but are almost inactive after 60 min of Ca2+ deprivation. It is concluded that a fraction of the myotropic effect of both NA and ATII is independent of external Ca2+. Readdition of Ca2+ (1.5 mM) at the peak of the residual effects obtained in absence of Ca2+ restores full control response to both agents. When the same intervention is repeated at different times after washout of the drug only the strips treated with ATII show a progressively decreasing contractile response. This indicates that ATII remains in the active form in the proximity of the receptors for several minutes after washing, while NA does not.The administration of the antagonists (8-Gly-ATII for ATII and phentolamine for NA) or the removal of external Ca2+ while maintaining the infusion of the two stimulants is followed by relaxations more rapid than that produced by the washout of ATII, but not of NA. A good correlation has been shown to exist between the rates of the relaxations induced by 8-Gly-ATII and the pD2 values of various angiotensins.The results suggest that the major difference between the actions of ATII and NA in rabbit aortae resides in the duration of the drug−receptor interaction. The drug−receptor complex of the peptide appears to be more stable than that of the catecholamine and this may explain the higher (with respect to NA) affinity of ATII for its aortic receptors.