title: Analysis of responses to angiotensin peptides in the hindquarters vascular bed of the cat.
abstract: Responses to angiotensin I, II, III, and IV, des-Asp1-angiotensin I, and (p-amino-Phe6)-angiotensin II were compared in the hindquarters vascular bed of the cat. The peptides produced dose-related increases in perfusion pressure, and dose-response curves to all six peptides were parallel. Des-Asp1-angiotensin I, angiotensin I, II, and III produced similar increases in perfusion pressure and were approximately 300-fold more potent than (p-amino-Phe6)-angiotensin II, 100-fold more potent than angiotensin IV, 30-fold more potent than norepinephrine, and 10-fold more potent than U-46619. The time courses of the response to des-Asp1-angiotensin I, angiotensin I, II, and III were similar, and responses were not altered by a time-delay coil. DuP-532, an AT1 receptor antagonist, reduced responses to the six angiotensin peptides. PD-123,319 did not alter responses to the angiotensin peptides. The angiotensin-converting enzyme inhibitor captopril reduced responses to angiotensin I and des-Asp1-angiotensin I. These results show that des-Asp1-angiotensin I as well as angiotensin I, II, III, and IV have similar efficacy and that responses to the peptides and (p-amino-Phe6)-angiotensin II are mediated by AT1 receptors. These results suggest that AT2 receptors have little role in modulating responses and that angiotensin IV has a lower affinity for the AT1 receptor than does angiotensin II or III. The results also indicate that complete rapid local conversion of the substrates into active peptides occurs near the site of action within the hindquarters vascular bed.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Garrison
authors.forename: J A
authors.initials: JA
authors.lastname: Santiago
authors.forename: S Y
authors.initials: SY
authors.lastname: Osei
authors.forename: P J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000803:Angiotensin I / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester; D017942:Nitric Acid / Q000037:antagonists & inhibitors; D010646:Phentolamine / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D005466:Fluorocarbons
chemical_list: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D000803:Angiotensin I; D000804:Angiotensin II; D000805:Angiotensin III; D057911:Angiotensin Receptor Antagonists; D000809:Angiotensins; D016718:Arachidonic Acid; D001120:Arginine; D002216:Captopril; D007093:Imidazoles; D008469:Meclofenamic Acid; D019331:NG-Nitroarginine Methyl Ester; D017942:Nitric Acid; D010646:Phentolamine; D011450:Prostaglandin Endoperoxides, Synthetic; D011725:Pyridines; D013777:Tetrazoles; D013928:Thromboxane A2; D014662:Vasoconstrictor Agents; C069045:DuP 532; D005466:Fluorocarbons; C073402:PD 123319; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-