Nifedipine-induced coronary vasodilation in ischemic hearts is attributable to bradykinin- and NO-dependent mechanisms in dogs

Masafumi Kitakaze, Hiroshi Asanuma, Seiji Takashima, Tetsuo Minamino, Yasunori Ueda, Yasuhiko Sakata, Masanori Asakura, Shoji Sanada, Tsunehiko Kuzuya, Masatsugu Hori

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

Background - Dihydropyridine calcium channel blockers protect endothelial cells against ischemia and reperfusion injury, suggesting that nifedipine may increase the in vivo cardiac NO level and thus coronary blood flow (CBF) in ischemic hearts. We tested this hypothesis. Methods and Results - In open-chest dogs, coronary perfusion pressure (CPP) was reduced in the left anterior descending coronary artery so that CBF decreased to one third of the control level, and thereafter CPP was maintained constant (103±8 to 43±3 mm Hg, n=9). We obtained fractional shortening (FS) and lactate extraction ratio (LER) as indices of regional myocardial contraction and metabolism. Both FS (26.4±2.1% to 6.7±2.0%, n=9, P<0.001) and LER (32±6% to -37±5%, n=9, P<0.001) showed a decrease when CPP was reduced. After intracoronary infusion of nifedipine (4 μg · kg-1 · min-1), CBF increased from 30±1 to 48±4 mL · 100 g-1 · min-1 (P<0.01) without a change of CPP (n=9). Both FS (14.0±1.9%, n=9) and LER (-9±7%, n=9) also increased (P<0.01). Nifedipine increased the difference in the level of metabolites of NO (nitrate+nitrite; 9±3 to 25±5 nmol/mL, n=9, P<0.01) and bradykinin (22±5 to 58±4 pmol/mL, n=9, P<0.01) between coronary venous and arterial blood. L-NAME (an NO synthase inhibitor) or HOE-140 (a bradykinin receptor antagonist) attenuated (P<0.05) the increase in CBF (29±3 and 35±2 mL · 100 g-1 · min-1, n=5 each), FS (4.8±0.6% and 6.9±1.7%, n=5 each), LER (-47±8% and -35±9%, n=5 each), and nitrate+nitrite (3±2 and 8±4 nmol/mL, n=5 each) due to nifedipine infusion. Conclusions - These results indicate that the calcium channel blocker nifedipine mediates coronary vasodilation and improves myocardial ischemia through both bradykinin/NO-dependent and -independent mechanisms.

Original languageEnglish
Pages (from-to)311-317
Number of pages7
JournalCirculation
Volume101
Issue number3
DOIs
Publication statusPublished - 2000 Jan 25

Keywords

  • Blood flow
  • Bradykinin
  • Ischemia
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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