title: Analysis of responses to angiotensin I (3-10) and Leu3 angiotensin (3-8) in the pulmonary vascular bed of the cat.
abstract: Pulmonary vascular responses to angiotensin (3-8) (Ang IV), leu3 angiotensin (3-8) (LeuAng IV), an Ang IV analog and angiotensin I (3-10) [Ang I (3-10)], the precursor for Ang IV, were investigated in the intact-chest cat under conditions of controlled blood flow. Intralobar injections of Ang IV, LeuAng IV, and Ang I (3-10) caused dosage-related increases in lobar arterial pressure. When responses were compared, Ang IV, LeuAng IV, and Ang I (3-10) were equipotent and were approximately 100- to 300-fold less potent than Ang II when dosages are expressed on a nanomolar basis. DuP 753, an angiotensin II type 1 (AT1 ) receptor antagonist, attenuated pulmonary vasoconstrictor responses to LeuAng IV, Ang IV, and its precursor, Ang I (3-10), but did not significantly change pressor responses to serotonin, norepinephrine, or U46619. PD 123319, an angiotensin II type 2 (AT2 ) receptor antagonist, and WSU 3033, a putative angiotensin II type 4 (AT4 ) receptor antagonist, did not significantly change pressor responses to LeuAng IV, Ang IV, and its precursor, Ang I (3-10). Captopril, an angiotensin-converting enzyme (ACE) inhibitor, decreased pulmonary vasoconstrictor responses to Ang I (3-10) but did not significantly change responses to serotonin, norepinephrine, U46619, LeuAng IV, or Ang IV. These data show that LeuAng IV, Ang IV, and its precursor, Ang I (3-10), increase pulmonary vascular resistance by activating AT1 receptors, and that Ang I (3-10) is rapidly and efficiently converted by an ACE-dependent pathway into an active peptide. The present data suggest that Ang IV and LeuAng IV increase pulmonary vascular resistance by activating AT1 receptors and that activation of AT2 or AT4 are not involved in mediating or modulating responses to these peptides. These data provide support for the hypothesis that Ang I (3-10) is converted into an active peptide by ACE at or near the site of action within the pulmonary vascular bed.
authors: Department of Anesthesiology, Tulane University Medical Center, 1430 Tulane Avenue, Box SL-4, New Orleans, LA 70112-2699, USA.
authors: A D
authors: AD
authors: Kaye
authors: B D
authors: BD
authors: Nossaman
authors: D E
authors: DE
authors: Smith
authors: I N
authors: IN
authors: Ibrahim
authors: M
authors: M
authors: Anwar
authors: P J
authors: PJ
authors: Kadowitz
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology
chemical_list: D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D000803:Angiotensin I; D002216:Captopril; D019808:Losartan