ACTIONS OF DES-ASP-ANGIOTENSIN-I ON THE AORTIC RINGS OF THE NORMO-TENSIVE AND HYPERTENSIVE RATS

The actions of des-Asp-angiotensin I, a nine aminoacid peptide, on the contractility of the aortic rings of the normotensive Wistar Kyoto ra ts (WKY) and spontaneously hypertensive rats (SHR) were studied. In th e presence of captopril which prevented its degradation to angiotensin III by angiotensin converting enzyme, des-Asp-angiotensin I exerted d irect concentration-dependent contractile action on the aortic rings. The contractile action was concentration-dependently attenuated by the AT(1) receptor antagonist, losartan, but was not affected by the AT(2 ) receptor antagonist, PD123319; indicating that angiotensin AT(1) rec eptors mediate the direct contractile action. The response to des-Asp- angiotensin I was qualitatively different from that to angiotensin III i.e. lower potency and a likely higher efficacy suggesting that the t wo angiotensins act on different subtypes of angiotensin receptor. The response of the aortic rings to angiotensin III and des-Asp-angiotens in I in the SHR was significantly lower than the corresponding respons es in the WKY. Des-Asp-angiotensin I attenuated in a concentration-dep endent and U-shape manner the response of the aortic ring to angiotens in III in the SHR but not in the WKY. Significant attenuation occurred in the pico to nano molar range of des-Asp-angiotensin I which is wit hin the physiological concentration of the nonapeptide. Although these findings are the first demonstration of a direct and modulatory actio n of des-Asp-angiotensin I on the blood vessels of the SHR and raise t he possibility of its involvement in blood pressure control, its exact role remains to be further studied.