Ja. Santiago et al., ANALYSIS OF RESPONSES TO BRADYKININ - EFFECTS OF HOE-140 IN THE HINDQUARTERS VASCULAR BED OF THE CAT, The American journal of physiology, 267(2), 1994, pp. 80000828-80000836
The mechanisms and receptor subtype mediating vasodilator responses to
bradykinin were investigated in the hindquarters vascular bed of the
cat under constant flow conditions. Intraarterial injections of bradyk
inin in doses of 10-1,000 ng into the hindquarters vascular bed caused
dose-related decreases in perfusion pressure that were inhibited by H
oe-140, a bradykinin Bz-receptor antagonist. Injections of des-Arg(9)-
bradykinin (in doses 10-fold higher than for bradykinin) caused smalle
r dose-related decreases in hindquarters perfusion pressure that were
not blocked by Hoe-140. Administration of atropine, glibenclamide, or
cyclooxygenase inhibitors did not alter vasodilator responses to brady
kinin, suggesting that activation of muscarinic receptors, ATP-sensiti
ve K+ channels, or prostaglandin release is not involved in the respon
se to the peptide. Administration of N-omega-nitro-L-arginine and its
methyl ester reduced vasodilator responses to bradykinin, acetylcholin
e, and substance P, whereas responses to endothelium-independent vasod
ilator agents were not attenuated. Decreases in systemic arterial pres
sure and in hindquarters perfusion pressure in response to bradykinin
were enhanced by the angiotensin-converting enzyme inhibitors captopri
l and enalaprilat. These results suggest that hindquarters vasodilator
responses to bradykinin are mediated by activation of kinin B-2 recep
tors and in part by the release of nitric oxide. These data also sugge
st the presence of bradykinin B-1 receptors, mediating vasodilation in
the hindquarters vascular bed. These results indicate that bradykinin
is rapidly inactivated by angiotensin-converting enzyme in the lung a
nd in the hindquarters vascular bed of the cat.