The aim of this study was to examine the effects of noradrenaline (NA) and prostaglandin F2 alpha (PGF2 alpha) on angiotensin II (AII)-induced contraction and tachyphylaxis in aortic rings of the rat. Neither NA (10(-9) M) nor PGF2 alpha (10(-7) M) had significant effect on the response of the rings to the spasmogenic concentrations (10(-10) to 10(-7) M) of AII, but lowered significantly the threshold response of the aortic rings to AII (from 10(-9) to 10(-12) M). In rings that were tachyphylatic to AII, both NA and PGF2 alpha attenuated significantly the tachyphylaxis of the rings to AII at the concentrations of 10(-10) and 10(-7) of the octapeptide; and also lowered the threshold of the tachyphylatic rings to AII (from 10(-9) to 10(-11) M for NA, and from 10(-9) to 10(-10) M for PGF2 alpha). The specific properties of noradrenaline and PGF2 alpha were not shared by the non-specific potassium chloride. Because the lowering of threshold and attenuation of tachyphylaxis occurred at the physiological levels of AII and NA, it is possible that the in vivo actions of AII are under constant modulation by circulating and localised (higher than circulating) levels (e.g. of PGF2 alpha) of spasmogens. The results also call into question the physiological significance of angiotensin tachyphylaxis and may suggest that it is only an in vitro phenomenon occurring in the absence of endogeneous spasmogens.
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