This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rowe, B. P. Articles by Dixon, B. Search for Related Content PubMed PubMed Citation Articles by Rowe, B. P. Articles by Dixon, B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LOSARTAN POTASSIUM Related Collections ACE/Angiotension receptors Animal models of human disease Other hypertension Hypertension - basic studies

(Hypertension. 2000;35:130.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Angiotensin III Depressor Action in the Conscious Rabbit Is Blocked by Losartan but not PD 123319

Brian P. Rowe; Byron Dixon

From the Department of Physiology, East Tennessee State University College of Medicine, Johnson City.

Correspondence to Brian P. Rowe, PhD, Department of Physiology, Box 70,576, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-0576. E-mail rowe{at}etsu.edu

Abstract—Vasodilator and vasodepressor properties of angiotensins have been reported, and mediation by prostaglandins or nitric oxide has been proposed. Other studies indicate that angiotensin AT₂ receptors might mediate a depressor action, and the present study was designed to delineate and explore this possibility in a conscious rabbit model. Large intravenous boluses of angiotensin III (15 nmol/kg) produced a predictable pressor peak (82±4 mm Hg) followed by a depressor phase (20±3 mm Hg), whereas equipressor doses of angiotensin II were less effective at producing depressor responses. Angiotensin-(1–7) did not exert a depressor action, and the reduced potency of angiotensin IV (relative to angiotensin III) was similar for both the pressor and depressor phases (100-fold). It is clear that specific angiotensin IV or angiotensin-(1–7) receptors do not mediate depressor effects in this model. The AT₁ antagonist losartan (1 mg/kg) blocked both the pressor and depressor components of the angiotensin III response, whereas the AT₂ antagonist PD 123319 (35 mg/kg) had no effect on either element of the response. The data obtained with the angiotensin receptor subtype–selective compounds, losartan and PD 123319, suggest that the depressor action is an AT₁-mediated effect and give no indication that AT₂ receptors could be involved. Paradoxically, the greater potency of angiotensin III as a vasodepressor belies the conclusion that the response is AT₁-mediated, because AT₁ receptors have a greater affinity for angiotensin II versus angiotensin III.

Key Words: angiotensin III • receptors, angiotensin • blood pressure • rabbits • losartan

This article has been cited by other articles:

				N. Toda, K. Ayajiki, and T. Okamura Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation Pharmacol. Rev., March 1, 2007; 59(1): 54 - 87. [Abstract] [Full Text] [PDF]