Angiotensin III Depressor Action in the Conscious Rabbit Is Blocked by Losartan but not PD 123319
Document Type
Article
Publication Date
1-1-2000
Description
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.
Citation Information
Rowe, Brian P.; and Dixon, Byron. 2000. Angiotensin III Depressor Action in the Conscious Rabbit Is Blocked by Losartan but not PD 123319. Hypertension. Vol.35(1). 130. https://doi.org/10.1161/01.HYP.35.1.130 PMID: 10642287 ISSN: 0194-911X