Fujiko Okabe

Inhibition of rat vascular smooth muscle proliferation in vitro and in vivo by bone morphogenetic protein-2.

Vascular proliferative disorders are characterized by the proliferation of vascular smooth muscle cells (SMCs) and excessive extracellular matrix synthesis. We found that bone morphogenetic protein-2 (BMP-2) inhibited serum-stimulated increases in DNA synthesis and cell number of cultured rat arterial SMCs in a fashion quite different from that in the case of transforming growth factor-beta1 (TGF-beta1). In addition, TGF-beta1 stimulated collagen synthesis in SMCs, whereas BMP-2 did not. In an in vivo rat carotid artery balloon injury model, the adenovirus-mediated transfer of the BMP-2 gene inhibited injury-induced intimal hyperplasia. These results indicate that BMP-2 has the ability to inhibit SMC proliferation without stimulating extracellular matrix synthesis, and suggest the possibility of therapeutic application of BMP-2 for the prevention of vascular proliferative disorders.

Hemodynamic effects of nifedipine in congestive heart failure

Nifedipine, a potent coronary vasodilator, was administered in a single sublingual dose of 20 mg to eight patients with mild to moderate congestive heart failure. Nifedipine produced a slight increase in heart rate (mean +/- standard error of the mean 73.3 +/- 3.2 versus 80.9 +/- 2.1 beats/min, p < 0.025) and an increase in cardiac index (from a control value of 3.51 +/- 0.22 to 4.06 +/- 0.31 liters/min per m2, p < 0.01). Arterial blood pressure decreased from 112.9 +/- 6.2/67.7 +/- 4.2 (mean 84.9 +/- 4.0) to 100.8 +/- 4.4/56.4 +/- 11.0 (mean 76.1 +/- 4.3) mm Hg (p < 0.01) and total systemic vascular resistance also decreased from a control value of 15.6 +/- 1.0 to 12.4 +/- 0.8 units (p < 0.01) after administration of nifedipine. These data suggest that nifedipine may be useful for vasodilation in congestive heart failure.

Effect of long-term cyclic mechanical load on protein synthesis and morphological changes in cultured Myocardial cells from neonatal rat

SummaryWe studied the effect of prolonged cyclic mechanical stimulation on protein synthesis and morphological changes in cultured cardiac myocytes isolated from 3-day-old neonatal rats to develop an in vitro model for cardiac hypertrophy induced by a mechanical load. Myocardial cells were cultured on deformative culture plates with M-199 culture medium in the presence or absence of fetal calf serum (FCS), and a cyclic mechanical load was applied for 2 hours up to 15 days. Mechanical stimulation for 2 hours increased the14C-phenylalanine incorporation rate of myocardial cells, both in the absence and presence of FCS or when the myocardial cells were either beating or arrested with tetrodotoxin. The incorporation rate always increased by mechanical stimulation during 15 days of cell culture as compared to cells that sustained no mechanical stress. The cell size and protein content, which increased gradually with mechanical stimulation and reached a maximum at 10 days, were even greater in the presence of FCS. Within 10 days myocardial cells had aligned in the direction of the maximal cyclic mechanical load. In these cells electron microscopy revealed an increase in the number of myofilaments associated with the development of mitochondria as recognized in the adult myocardial cells. These results indicate that long-term cyclic mechanical loading of cultured myocardial cells may be a good in vitro model for the study of cardiac hypertrophy.