Blood pressure responses to acute or chronic captopril in mice with disruption of bradykinin B2-receptor gene.
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.


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).


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.
Emanueli
C
C
Institute of Pharmacology, University of Sassari, Italy.
Angioni
G R
GR
Anania
V
V
Spissu
A
A
Madeddu
P
P
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D017353:Gene Deletion; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C065679:icatibant; D002216:Captopril; D001920:Bradykinin