Back to Search
Start Over
Blood pressure responses to acute or chronic captopril in mice with disruption of bradykinin B2-receptor gene.
- Source :
-
Journal of hypertension [J Hypertens] 1997 Dec; Vol. 15 (12 Pt 2), pp. 1701-6. - Publication Year :
- 1997
-
Abstract
- Objective: To evaluate the role of kinins in the hypotensive response to angiotensin converting enzyme inhibition, we compared the blood pressure effects induced by acute or chronic captopril administration in a mouse strain (Bk2r-/-) with disruption of the bradykinin B2 receptor gene and in wild-type controls (J129 Sv mice). A second aim was to determine whether Icatibant, a selective bradykinin B2-receptor antagonist, prevented the blood pressure changes induced by acute captopril administration in Swiss, c57/B16, J129 Sv and Bk2r-/- mice.<br />Methods and Results: Under basal conditions, tail-cuff systolic blood pressure (SBP) and intra-arterial mean blood pressure (MBP) were higher in Bk2r-/- than in J129 Sv (SBP: 132+/-2 versus 113+/-3 mmHg; MBP: 144+/-6 versus 122+/-10 mmHg, P< 0.05 for both comparisons). Acute captopril administration (1 mg/kg body weight, intra-arterially) reduced the MBP of Bk2r-/- and J129 Sv by 36+/-8 and 31+/-7 mmHg, respectively. Swiss and c57/B16 mice showed similar decreases in MBP following captopril. Pretreatment with Icatibant (10 nmol/kg body weight, intra-arterially) did not influence the MBP responses to acute captopril in all the strains. Chronic administration of captopril (approximately 120 mg/kg body weight per day for 2 weeks in drinking water) reduced SBP in either Bk2r-/- or J129 Sv. The magnitude of this response was higher in Bk2r-/- than in J129 Sv (65+/-3 versus 47+/-4 mmHg, respectively, P < 0.01).<br />Conclusions: Our results suggest that endogenous kinins do not participate in the hypotensive response to angiotensin converting enzyme inhibition in mice; in Bk2r-/-, the exaggerated blood pressure response to chronic captopril appears to be attributable to interference with unbalanced vasoconstrictor action of the renin-angiotensin system.
- Subjects :
- Adrenergic beta-Antagonists administration & dosage
Adrenergic beta-Antagonists pharmacology
Animals
Bradykinin administration & dosage
Bradykinin analogs & derivatives
Bradykinin pharmacology
Bradykinin Receptor Antagonists
Dose-Response Relationship, Drug
Drug Administration Routes
Hypertension metabolism
Male
Mice
Mice, Knockout genetics
Receptor, Bradykinin B2
Receptors, Bradykinin genetics
Vasoconstriction drug effects
Angiotensin-Converting Enzyme Inhibitors pharmacology
Blood Pressure drug effects
Captopril pharmacology
Gene Deletion
Hypertension physiopathology
Receptors, Bradykinin physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0263-6352
- Volume :
- 15
- Issue :
- 12 Pt 2
- Database :
- MEDLINE
- Journal :
- Journal of hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 9488225
- Full Text :
- https://doi.org/10.1097/00004872-199715120-00075