Reduced coronary vasodilator responses to amlodipine in pacing-induced heart failure in conscious dogs: role of nitric oxide.
1. This study examined whether NO is involved in the in-vivo coronary vasodilator effects of amlodipine (a calcium channel blocker) and whether heart failure (HF) alters the coronary responses to amlodipine. 2. Nine conscious dogs were chronically instrumented to measure circumflex coronary blood flow (CBF) and coronary diameter (CD). Drugs were administered directly into the circumflex artery through an indwelling catheter to avoid systemic changes. HF was induced by right ventricular pacing (240 b.p.m., 3 weeks). 3. Compared with control (C), in HF, coronary responses to acetylcholine (1 - 10 ng kg(-1)) were reduced while responses to nitroglycerin (0.1 - 0.5 microg kg(-1)) were unchanged. In C, amlodipine (30 - 150 microg kg(-1)), increased dose-dependently CBF and CD. After LNA (a NO synthase inhibitor, 2 mg kg(-1)), amlodipine produced less increases in CBF and CD (+121+/-26 ml min(-1) and +76+/-35 microm versus +196+/-40 ml min(-1) and +153+/-39 microm respectively for 150 microg kg(-1) amlodipine alone, both P<0.05). In HF, the coronary responses to amlodipine were reduced (150 microg kg(-1) of amlodipine increased CBF and CD +121+/-23 ml min(-1) and +77+/-21 microm respectively, both P<0.05). After LNA, the CBF responses to amlodipine tended to be reduced (+94+/-19 ml min(-1) at 150 microg kg(-1)) but CD responses were significantly reduced (+41+/-16 microm, P<0.05). The supplementation with L-arginine did not enhance the coronary responses to amlodipine. 4. These results indicate that, in conscious dogs, NO participates in the coronary responses to amlodipine and in HF, the coronary responses to amlodipine are reduced, which is related to a reduced NO production.
Champagne
Stéphane
S
INSERM U400, Faculté de Médecine, 94010 Créteil, France.
Hittinger
Luc
L
Héloire
François
F
Suto
Yukio
Y
Sambin
Lucien
L
Crozatier
Bertrand
B
Su
Jin Bo
JB
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014851:Wakefulness / Q000502:physiology
D014665:Vasodilator Agents; D017311:Amlodipine; D009569:Nitric Oxide