RT Journal Article
SR Electronic
T1 Angiotensin Peptides Modulate Bradykinin Levels in the Interstitium of the Dog Heart in Vivo
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 324
OP 329
DO 10.1124/jpet.300.1.324
VO 300
IS 1
A1 Chih-Chang Wei
A1 Carlos M. Ferrario
A1 K. Bridget Brosnihan
A1 Diane M. Farrell
A1 Wayne E. Bradley
A1 Ayad A. Jaffa
A1 Louis J. Dell'Italia
YR 2002
UL http://jpet.aspetjournals.org/content/300/1/324.abstract
AB We previously demonstrated the substantial capacity for angiotensin (ANG) II formation in the interstitium of the dog heart in vivo. The current study tested the hypothesis that interstitial fluid (ISF) bradykinin (BK) is influenced by ANG II formation. Four microdialysis probes were inserted into the left ventricular myocardium of eight open-chest anesthetized dogs. The probe effluent was collected during four stages in each dog. Probes 1 and 3 sequentially delivered: 1) buffer; 2) ANG I (15 μM); 3) ANG II type 1 receptor antagonist (AT1-ant; irbesartan, 50 μM) or AT2-ant (PD123319, 50 μM); and 4) ANG I + AT1-ant or ANG I + AT2-ant. Probes 2 and 4 used the same protocol, substituting ANG II for ANG I in a concentration (0.5 μM) equivalent to that achieved during ANG I infusion. ISF BK levels increased 15-fold during ANG I (p < 0.001) but not during ANG II infusion. Co-infusion of selective AT1- and AT2-ants or nonselective AT-ant did not block the increase in ISF BK. ISF infusions of ANG I also produced a greater than 400-fold rise in ISF ANG-(1-7) over baseline. ISF infusion of ANG-(1-7) (10 μM) produced a 15-fold increase in ISF BK (p < 0.001). The metabolic machinery exists for the formation of BK and ANG-(1-7) in the cardiac ISF space that is not blocked by an AT receptor antagonist. The differential increase in ISF BK during ANG I and ANG-(1-7) but not during ANG II infusions suggests the possibility of decreased catabolism of ISF BK by an angiotensin-converting enzyme due to active site occupation by ANG I and ANG-(1-7). ANGangiotensinISFinterstitial fluidBKbradykininATANG typeAT1-antANG II type 1 receptor antagonistAT2 antANG II type 2 receptor antagonistACEangiotensin-converting enzymeRASrenin-angiotensin systemLVleft ventricular or left ventriclebpmbeats per minute