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

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 35; no. 1, Part 1; p. 130
• Main Authors: Rowe, Brian P, Dixon, Byron
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.01.2000; Hagerstown, MD Lippincott
• Subjects: Angiotensin I; Angiotensin II - analogs & derivatives; Angiotensin II - pharmacology; Angiotensin II - physiology; Angiotensin III - antagonists & inhibitors; Angiotensin III - pharmacology; Angiotensin III - physiology; Angiotensin Receptor Antagonists; Animals; Biological and medical sciences; Blood Pressure - drug effects; Blood Pressure - physiology; Blood vessels and receptors; Fundamental and applied biological sciences. Psychology; Imidazoles - pharmacology; Losartan - pharmacology; Male; Peptide Fragments - pharmacology; Pyridines - pharmacology; Rabbits; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin - physiology; Vertebrates: cardiovascular system; Animal model; Angiotensin III; Peptide hormone; Rabbit; Lagomorpha; Biological activity; Vasodilation; Renin angiotensin system; Vertebrata; Vasomotricity; Mammalia; Animal; Blood vessel; Circulatory system
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.35.1.130

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.