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Angiotensin-converting enzymeinhibitors and angiotensin iireceptor blockers synergistically increasecoronary blood flow in canine ischemic myocardium

Role of bradykinin

Masafumi Kitakaze, MD, FACC^*,*, Hiroshi Asanuma, MD, Hiroharu Funaya, MD, Koichi Node, MD, Seiji Takashima, MD, Shoji Sanada, MD, Masanori Asakura, MD, Hisakazu Ogita, MD, Jiyoong Kim, MD^* and Masatsugu Hori, MD, FACC

^* Cardiovascular Division of Internal Medicine, National Cardiovascular Center, Osaka University Graduate School of Medicine, Suita, Japan
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan

View larger version (25K): [in a new window]   Figure 1 Coronary blood flow (CBF) before the reduction of coronary perfusion pressure (C) and during myocardial ischemia with (I + Drug) or without (I) RNH-6270, temocaprilat or both. The results were obtained with saline (left), HOE140 (middle) or N-nitro-L-arginine methyl ester (L-NAME) (right) infusion.

View larger version (22K): [in a new window]   Figure 2 Nitric oxide (NOx) (cardiac NO2– + NO3–) level before the reduction of coronary perfusion pressure (C) and during myocardial ischemia with (I + Drug) or without (I) RNH-6270, temocaprilat or both. The results were obtained with saline (left), HOE140 (middle) or N-nitro-L-arginine methyl ester (L-NAME) (right) infusion.

View larger version (22K): [in a new window]   Figure 3 Cardiac bradykinin (BK) levels before the reduction of coronary perfusion pressure (C) and during myocardial ischemia with (I + Drug) or without (I) RNH-6270, temocaprilat or both. The results were obtained with saline (A), HOE140 (B) or N-nitro-L-arginine methyl ester (L-NAME) (C) infusion.

View larger version (27K): [in a new window]   Figure 4 Coronary blood flow before and during the infusion of three doses of bradykinin with and without either RNH-6270 or temocaprilat. RNH-6270 enhanced the bradykinin-induced increase in coronary blood flow. C = coronary perfusion pressure; Drug = with RNH-6270.