Actions of des-Asp angiotensin I on the aortic rings of the normo- 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 rats (WKY) and spontaneously hypertensive rats (SHR) were studied. In the presence of captopril which prevented its degradation to angiotensin III by angiotensin converting enzyme, des-Asp-angiotensin I exerted direct concentration-dependent contractile action on the aortic rings. The contractile action was concentration-dependently attenuated by the AT1 receptor antagonist, losartan, but was not affected by the AT2 receptor antagonist, PD123319; indicating that angiotensin AT1 receptors 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 two angiotensins act on different subtypes of angiotensin receptor. The response of the aortic rings to angiotensin III and des-Asp-angiotensin I in the SHR was significantly lower than the corresponding responses in WKY. Des-Asp-angiotensin I attenuated in a concentration-dependent and U-shape manner the response of the aortic ring to angiotensin 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 within the physiological concentration of the nonapeptide. Although these findings are the first demonstration of a direct and modulatory action of des-Asp-angiotensin I on the blood vessels of the SHR and raise the possibility of its involvement in blood pressure control, its exact role remains to be further studied.
Lim
B C
BC
Department of Pharmacology, Faculty of Medicine National University of Singapore.
Sim
M K
MK
D000803:Angiotensin I / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000804:Angiotensin II / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006973:Hypertension / Q000188:drug therapy*; D066298:In Vitro Techniques; D016015:Logistic Models; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects
D000804:Angiotensin II; D000805:Angiotensin III; C011437:angiotensin I, des-Asp(1)-; D000803:Angiotensin I