Bradykinin infusion in chronic cardiac failure and the effects of captopril.
BACKGROUND
Patients with chronic cardiac failure (CCF) have abnormal vascular responses. Bradykinin (BK) is thought to contribute to the vasodilator effects of ACE inhibitors, but the effect of BK itself in patients with CCF has not been examined.


METHODS
We studied the responses to infused BK at 10, 30 and 100 pmol min(-1) in patients with CCF (n=10) and controls (n=10). The slope of the dose-response curve was used for comparisons between the groups. Forearm blood flow (FBF) was measured by venous occlusion plethysmography.


RESULTS
Following BK, vasodilatation was observed in both groups as the slopes were positive in all, but the difference between the groups was not significant (P=0.77). The study was repeated with the co-administration of 4 micromol min(-1) of N(G)-monomethyl L-arginine (L-NMMA). The vasodilator response to BK was reduced in both groups, and the effect was somewhat greater in the patient group (P=0.23). The vasodilator response to the endothelium-independent vasodilator sodium nitroprusside was slightly less in the patient group (P=0.08). The patients only then underwent repeat infusion of BK before and after a single oral dose of captopril 12.5 mg or placebo. Following captopril, the vasodilator response to BK was unchanged when compared to placebo (difference between slopes, P=0.53).


CONCLUSIONS
BK produces dose-dependent vasodilatation in both patients with CCF and controls; there was no difference in the responses, which were antagonised by L-NMMA and therefore in part NO (endothelium)-dependent. The responses were also unchanged after administration of an ACE inhibitor (captopril).
Maguire
S M
SM
Department of Medicine, Royal Victoria Hospital, BT12 6BA, Belfast, UK.
McAuley
D
D
McGurk
C
C
Nugent
A G
AG
Johnston
G D
GD
Nicholls
D P
DP
D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001920:Bradykinin / Q000008:administration & dosage*; D002216:Captopril / Q000008:administration & dosage*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005542:Forearm / Q000098:blood supply; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D001920:Bradykinin