title: Angiotensin III depressor action in the conscious rabbit is blocked by losartan but not PD 123319.
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 AT(2) 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 ( approximately 100-fold). It is clear that specific angiotensin IV or angiotensin-(1-7) receptors do not mediate depressor effects in this model. The AT(1) antagonist losartan (1 mg/kg) blocked both the pressor and depressor components of the angiotensin III response, whereas the AT(2) 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 AT(1)-mediated effect and give no indication that AT(2) receptors could be involved. Paradoxically, the greater potency of angiotensin III as a vasodepressor belies the conclusion that the response is AT(1)-mediated, because AT(1) receptors have a greater affinity for angiotensin II versus angiotensin III.
authors.affiliation: Department of Physiology, East Tennessee State University College of Medicine, Johnson City, TN 37614-0576, USA. rowe@etsu.edu
authors.forename: B P
authors.initials: BP
authors.lastname: Rowe
authors.forename: B
authors.initials: B
authors.lastname: Dixon
mesh_terms: D000803:Angiotensin I; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D000805:Angiotensin III / Q000037:antagonists & inhibitors* / Q000494:pharmacology* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000805:Angiotensin III; C073402:PD 123319; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan