Ryouji Kouzuma

Angiotensin receptor blocker improves coronary flow velocity reserve in hypertensive patients: comparison with calcium channel blocker.

Large-scale clinical studies have indicated that angiotensin receptor blockers (ARBs) have beneficial effects against cardiovascular diseases. We designed this study to compare the effects of an ARB and a calcium channel blocker (CCB) on coronary flow velocity reserve (CFVR), a predictor of cardiovascular events, as estimated using transthoracic Doppler echocardiography. Sixteen hypertensive patients (63.1±9.6 years old; 10 males) were randomly allocated in a double-blind fashion to valsartan (n=8, 40–80 mg/day) or nifedipine (n=8, 20–40 mg/day) groups. Age- and gender-matched subjects without hypertension were enrolled as a control group (n=12). CFVR was calculated by dividing the adenosine triphosphate–induced hyperemic flow velocity by the basal flow velocity in the left anterior descending coronary artery. Baseline characteristics and reduction in systolic and diastolic blood pressure after 6 months were similar in both groups. CFVR in the valsartan group increased from 2.34±0.38 to 3.10±0.84 at 2 months (p<0.05), and to 3.04±1.09 at 6 months (p<0.01). Both values became comparable to that in the control group (2.81±0.60). CFVR in the valsartan group was significantly higher (p<0.001) than that in the nifedipine group, which was little changed at 6 months. This discrepancy was derived from the significant increase of hyperemic velocity in the valsartan group, from 36.6±17.3 cm/s to 41.1±12.7 cm/s at 2 months, and to 48.1±20.2 cm/s at 6 months. We concluded that the ARB valsartan not only reduced high blood pressure but improved CFVR in hypertensive patients. However, these effects were not seen with the CCB nifedipine.

Influence of coronary artery disease risk factors on baroreflex sensitivity in the elderly.

Abstract.In this study, we assessed whether baroreflex sensitivity (BRS) is influenced by risk factors of cardiovascular disease. Subjects of this study were 95 elderly people (40 males and 55 females; mean age ± SD, 66.6±1.6 years) who underwent a medical check-up. BRS was determined as the gain of transfer function in baroreflex arc by spectral analysis of mean blood pressure and R-R interval variabilities in low-frequency band (0.04–0.15 Hz). Gender-related differences in BRS and relationships between BRS and various risk factors of cardiovascular disease were investigated. The value of BRS was significantly higher in males [10.7±3.7 (SD) ms/mmHg] than in females [9.0±4.0 ms/mmHg, p< 0.05]. However, this gender-related difference disappeared when other variables were taken into account in the multivariate model. Multiple regression analyses showed independent inverse relationships between BRS and heart rate [b=–0.016±0.004 (SE) bpm, β=–0.39], and between BRS and platelet count [b=–0.002±0.001 × 103/µl, β=–0.22]. Our results indicated that BRS is inversely related to platelet count in the elderly population. The precise mechanism of this correlation is unknown, but platelet factors released from platelet aggregates can potentially influence vascular function and modify BRS, or there is a common underlying determinant responsible for the covariation.

Promotion of Aortic Smooth Muscle Cell Proliferation by Hypercholesterolemic LDL and Its Suppression by Heparin or Sulfated Glycosaminoglycans

The effects of low-density lipoprotein (LDL) from normolipidemic (NL) and familial hypercholesterolemic (FH) human subjects on the smooth muscle cell (SMC) proliferation were examined, along with the antiproliferative actions of heparin and glycosaminoglycans (GAGs) in this system. Cell growth was stimulated from 146 to 176% by FH-over NL-LDL. This proliferative effect of FH-LDL was accompanied by an increase in the membrane cholesterol content and an increase in Ca2+ influx. These effects of FH-LDL were partially inhibited (50%) following methylation of apoprotein B100· The effects of FH-LDL were abolished by heparin and sulfated GAGs and this inhibitory effect was also accompanied by normalization of Ca2+ influx and cell membrane cholesterol. Electrokinetic analysis demonstrated a reduced net negative charge of FH-LDL relative to that of NL-LDL. We hypothesize that LDL surface charge may regulate the movement of cholesterol into the SMC plasma membrane where its presence in excess alters SMC function. Taken together, these results implicate a role for FH-LDL cholesterol as an important factor in the alteration of SMC cell growth kinetics in hypercholesterolemia, a process which can be modulated by heparin and sulfated GAGs.