title: Angiotensin II type 1 receptor blockade prevents cardiac remodeling in bradykinin B(2) receptor knockout mice.
abstract: Knockout mice (B(2)(-/-)) lacking the bradykinin (BK) B(2) receptor gene develop mild hypertension, cardiac hypertrophy, and myocardial damage. We hypothesized that these effects are due to the hypertrophying and damaging actions of angiotensin II (Ang II) in the absence of the balancing protection of BK. To verify this hypothesis, B(2)(-/-) or wild-type mice (B(2)(+/+)) were administered a nonpeptide antagonist of Ang II type 1 (AT(1)) receptors (A81988) from conception through 180 days of age. Untreated B(2)(+/+) and B(2)(-/-) served as controls. Blood pressure (BP) and heart rate were monitored with the use of tail-cuff plethysmography at regular intervals. Ventricular weights, diameters, wall thickness, chamber volume, and myocardial fibrosis were measured at 40 and 180 days. No differences were observed in BP, heart rate, and cardiac weight and dimensions between treated and untreated B(2)(+/+). The BP of AT(1) antagonist-treated B(2)(-/-) was reduced until 70 days; then, it increased to the levels found in untreated B(2)(-/-). AT(1) receptor blockade resulted in a reduction in left ventricular mass, chamber volume, and wall thickness and abrogated myocardial fibrosis in B(2)(-/-). These results indicate that Ang II is the major factor responsible for ventricular remodeling and myocardial damage in mice with disruption of BK B(2) receptor signaling. The interaction of Ang II and BK appears to be essential for the development of a normal heart.
authors.affiliation: National Laboratory of the National Institute of Biostructures and Biosystems, Osilo, Italy. madeddu@yahoo.com
authors.forename: P
authors.initials: P
authors.lastname: Madeddu
authors.forename: C
authors.initials: C
authors.lastname: Emanueli
authors.forename: R
authors.initials: R
authors.lastname: Maestri
authors.forename: M B
authors.initials: MB
authors.lastname: Salis
authors.forename: A
authors.initials: A
authors.lastname: Minasi
authors.forename: M C
authors.initials: MC
authors.lastname: Capogrossi
authors.forename: G
authors.initials: G
authors.lastname: Olivetti
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000235:genetics / Q000473:pathology; D006339:Heart Rate; D006352:Heart Ventricles / Q000737:chemistry / Q000473:pathology; D006973:Hypertension / Q000235:genetics / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000737:chemistry* / Q000473:pathology*; D009539:Nicotinic Acids / Q000494:pharmacology; D009929:Organ Size; D010641:Phenotype; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D009539:Nicotinic Acids; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D013777:Tetrazoles; D000804:Angiotensin II; C081174:A 81988