(Circulation. 2000;101:1848.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Stimulation of Bradykinin B1 Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs
Comparison With B2 Receptor Stimulation
From INSERM U400, Faculté de Médecine, Créteil, France, and the Département de Pharmacologie (F.B., A.B.), Hôpital Kremlin-Bicêtre, Kremlin Bicêtre, France.
Correspondence to Luc Hittinger, MD, INSERM U400, Hôpital Léon Bernard, 94456 Limeil Brévannes, France. E-mail hittinger{at}im3.inserm.fr
Background—Constitutive bradykinin B1 receptors have been identified in dogs; however, their physiological implications involving the coronary circulation remain to be determined. This study examined, in conscious dogs, the coronary response to des-Arg9-bradykinin (a B1 receptor agonist) and the mechanisms involved.
Methods and Results—Eleven dogs were instrumented with a left
ventricular micromanometer, a
circumflex coronary catheter, a cuff occluder, a Doppler
flow probe, and ultrasonic crystals to measure coronary blood
flow velocity (CBFv) and coronary diameter (CD).
Intracoronary des-Arg9-bradykinin (3 to 100 ng/kg)
and bradykinin (0.1 to 10 ng/kg) did not modify systemic
hemodynamics but dose-dependently increased CBFv and
CD. Des-Arg9-bradykinin was less potent than bradykinin.
Hoe 140 (a B2 antagonist, 10 µg/kg) abolished
the effects of bradykinin but did not influence the effects of
des-Arg9-bradykinin. When CBFv increase was prevented by
the cuff occluder, CD responses to bradykinin and
des-Arg9-bradykinin were maintained. Intracoronary
lisinopril (0.75 mg) increased the CD response to
bradykinin, with only minimal effect on CBFv, and extended the duration
of the effect. Lisinopril did not alter
des-Arg9-bradykinin responses. Intracoronary
N
-nitro-L-arginine (2 mg/kg)
decreased the CD effect of bradykinin and prevented the CBFv and CD
effects of des-Arg9-bradykinin. The relaxing effect of
des-Arg9-bradykinin on isolated coronary rings was
prevented by
des-Arg9,[Leu8]-bradykinin.
Conclusions—In the conscious dog, B1 receptors are present in coronary vessels, and their stimulation produces vasodilation in conductance and resistance vessels, which is mediated essentially by NO but not modulated by angiotensin-converting enzyme. However, the coronary vasodilation induced by B1 receptor stimulation is not as great as that produced by B2 receptor stimulation.
Key Words: bradykinin • nitric oxide • receptors • vasodilation
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