Angiotensin III and IV activation of the brain AT1 receptor subtype in cardiovascular function |
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Authors: | John W. Wright Anita J. Bechtholt Shelley L. Chambers Joseph W. Harding |
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Affiliation: | * Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA † Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-4820, USA ‡ College of Pharmacy, Washington State University, Pullman, WA 99164-4820, USA |
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Abstract: | The present investigation determined that native angiotensins II and III (ANG II and III) were equipotent as pressor agents when ICV infused in alert rats, whereas native angiotensin IV (ANG IV) was less potent. An analogue of each of these angiotensins was prepared with a hydroxyethylamine (HEA) amide bond replacement at the N-terminus, yielding additional resistance to degradation. These three angiotensin analogues, HEA-ANG II, HEA-ANG III, and HEA-ANG IV, were equivalent with respect to maximum elevation in pressor responses when ICV infused; and each evidenced significantly extended durations of effect compared with their respective native angiotensin. Comparing analogues, HEA-ANG II had a significantly longer effect compared with HEA-ANG III, and HEA-ANG IV, whereas the latter were equivalent. Pretreatment with the AT1 receptor subtype antagonist, Losartan (DuP753), blocked subsequent pressor responses to each of these analogues, suggesting that these responses were mediated by the AT1 receptor subtype. Pretreatment with the specific AT4 receptor subtype antagonist, Divalinal (HED 1291), failed to influence pressor responses induced by the subsequent infusion of these analogues. These results suggest an important role for Ang III, and perhaps ANG IV, in brain angiotensin pressor responses mediated by the AT1 receptor subtype. |
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Keywords: | Angiotensin II Angiotensin III Angiotensin IV Angiotensin analogues Blood pressure regulation Receptor subtypes DuP753 Divalinal Intracerebroventricular infusion Rats |
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