Shuji Mukae

Bradykinin B2 Receptor Gene Polymorphism Is Associated With Angiotensin-Converting Enzyme Inhibitor–Related Cough

The appearance of cough in association with angiotensin-converting enzyme (ACE) inhibitors is thought to be related to bradykinin, and it has been speculated that the elicitation of adverse effects is genetically predetermined. Several polymorphisms of the human bradykinin B(2) receptor gene may be involved in ACE inhibitor-related cough. To investigate this possibility, we identified the -58 thymine (T)/cytosine (C) polymorphism in subjects with ACE inhibitor-related cough. We classified the study population into 4 groups: subjects with and without cough that were treated with ACE inhibitors (n=30/30), nontreated essential hypertensive subjects (n=100), and normotensive subjects (n=100). The -58T/C was genotyped by the polymerase chain reaction single-strand conformation polymorphism method. The frequencies of the CC genotype and C allele of -58T/C were significantly higher in the nontreated hypertensive subjects than in the normotensive subjects. Conversely, the frequencies of the TT genotype and T allele were significantly higher in the subjects with cough than in the subjects without cough. These tendencies were more pronounced in females. Among the promoter assays of the human bradykinin B(2) receptor, -58T was found to have a higher transcription rate than that of -58C. This finding seems to suggest that the transcriptional activity of promoter might be involved in the appearance of ACE inhibitor-related cough. A genetic variant of the bradykinin receptor is involved in the elicitation of ACE inhibitor-related cough. It may be possible to predict the side effects of ACE inhibitors in advance.

Congestive heart failure is associated with the rate of bone loss

Abstract.  Nishio K, Mukae S, Aoki S, Itoh S, Konno N, Ozawa K, Satoh R, Katagiri T (School of Medicine Showa University, Hatanodai, Shinagawa‐ku, Tokyo, Japan). Congestive heart failure is associated with the rate of bone loss. J Intern Med 2003; 253: 439–446.

Effects of Catecholamine and Amrinone on the Metabolism of Noninfarcted Myocardium in Cardiogenic Shock

We investigated the effects of catecholamine and amrinone (AMR) on the metabolism of noninfarcted myocardium (NIM) during heart failure in acute myocardial infarction. Acute myocardial ischemia was induced by left circumflex coronary artery ligation on dogs divided into two groups: in the C group, left ventricular pressive (LVP) remained at >70% and in the S group, LVP decreased to <70% of preligation values. In part of the S group, 10 μg/kg/min of dopamine (DOA) or dobutamine (DOB), or 60μg/kg/min of AMR, were given intravenously beginning 90 min after ligation. At the end of 120 min of ischemia, mitochondria were extracted from NIM, and respiratory and electron transport system enzyme activities were measured. In the DOA and DOB groups, LVP, myocardial blood flow, cardiac output, and max LV dp/dt recovered significantly. In the AMR group, in spite of LVP reduction, other hemodynamic parameters increased. In the S group, state III respiration, complex I, and DNP-ATPase activities in NIM decreased to 62%, 65%, and 68% of preligaton levels, respectively. These values improved markedly with DOA, DOB, and AMR treatments. Electron microscopy showed swelling and fusion of mitochondria in the S group. These results indicate that catecholamine and AMR improve energy production in NIM and ultimately improve cardiac function.

Metabolic Changes in Nonischemic Myocardium During Pump Failure

Metabolic changes in the nonischemic myocardium after acute myocardial infarction in canine hearts were studied. Ca2+-ATPase activity and the major ATPase protein of the sarcoplasmic reticulum, tissue levels of ATP, mitochondrial respiratory, and complex I activities were decreased in the noninfarcted zone in proportion to heart function. It is suggested that recovery of these functions may be important in any treatment of pump failure.