We have investigated the effect of interleukin 6 (IL-6) on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortas. Murine recombinant IL-6 significantly increased the number of VSMC and stimulated tritiated thymidine incorporation into VSMC in a dose-dependent manner. The IL-6-induced thymidine incorporation into VSMC was totally inhibited by the Ca2+ channel blocker verapamil; however, IL-6 showed no effects on the intracellular Ca2+ level ([Ca2+]i) in VSMC. Antibody against platelet-derived growth factor (PDGF) also totally inhibited the IL-6-induced thymidine uptake. PDGF caused a significant increase in the [Ca2+]i, which was totally inhibited by verapamil. IL-6 mRNA was not detected in unstimulated "quiescent" VSMC, but its expression was stimulated by exposure of VSMC to 10% fetal bovine serum. Immunohistochemical study using anti-PDGF antibody showed that IL-6 stimulated PDGF production in VSMC. These results support the premise that IL-6 is released by VSMC in an autocrine manner and promotes the growth of VSMC via induction of endogenous PDGF production.

The present study investigates whether lower-limb dominant exercise training in patients with chronic heart failure (CHF) improves endothelial function primarily in the trained lower extremities or equally in the upper and lower extremities. Twenty-eight patients with CHF were randomized to the exercise or control group. The exercise group underwent cycle ergometer training for 3 months while controls continued an inactive sedentary lifestyle. Exercise capacity (6-min walk test) and flow-mediated vasodilation in the brachial and posterior tibial arteries were evaluated. After 3 months, walking performance increased only in the exercise group (488+/-16 to 501+/-14 m [control]; 497+/-23 to 567+/-39 m [exercise, p<0.05]). The flow-mediated vasodilation in the brachial arteries did not change in either group (4.2+/-0.5 to 4.5+/-0.4% [control]; 4.3+/-0.5 to 4.6+/-0.4% [exercise]), but that in the posterior tibial arteries increased only in the exercise group (4.1+/-0.5 to 4.1+/-0.3% [control]; 3.6+/-0.3 to 6.4+/-0.6% [exercise, p<0.01]). Cycle ergometer training improved flow-mediated vasodilation in the trained lower limbs, but not in the untrained upper limbs. Exercise training appears to correct endothelial dysfunction predominantly by a local effect in the trained extremities.

No abstract

Objective: To compare the effects of nicorandil (a hybrid ATP sensitive potassium channel (K + ATP channel) opener/nitric oxide donor) with those of isosorbide dinitrate (ISDN) on myocardial microcirculation and cardiac function in patients with acute myocardial infarction (AMI) who had undergone reperfusion treatment by direct balloon angioplasty. Design: Double blind randomised study. Patients: 60 patients with AMI in Killip class I. Interventions: Patients were assigned into two treatment groups: a nicorandil group (n = 30) and an ISDN group (n = 30). Each drug was infused intravenously at 6 mg/h for 72 hours starting at admission and was administered directly to the treated coronary artery immediately after angioplasty. Results: Compared with ISDN, nicorandil more frequently caused recovery of ST segment elevation just after reperfusion (15 of 27 (55.5%) in the nicorandil group v 5 of 26 (19.2%) in the ISDN group, p = 0.006). The nicorandil group had higher values of averaged peak velocity 40 minutes after reperfusion (mean (SD) 24.8 (13.3) cm/s v 16.0 (11.1) cm/s, p = 0.045) and higher values of regional wall motion of the infarcted area three weeks after onset of AMI (-1.78 (1.11) v -2.50 (1.04) SD/chord, p = 0.046). Conclusions: A combination of nicorandil drip infusion starting before reperfusion and intracoronary injection immediately after reperfusion is more effective than a similarly performed infusion of ISDN in preserving myocardial microcirculation in the reperfused AMI area. The nicorandil regimen resulted in better left ventricular regional wall motion.

Na,K-ATPase (NaK-pump) plays an important role in the regulation of intracellular ion composition. The purpose of this study is to determine whether Na' regulates the levels of mRNA coding for NaK-ATPase a and fi subunits in cultured neonatal rat cardiocytes. We measured intracellular Na+ levels (QNa'Ij) in cardiocytes using a Na'-sensitive fluorescence dye (SBFI). 1 mM ouabain caused a significant increase in [Nalji in cardiocytes; from 12.8±03 to 28.8±1.8 mM. Exposure of cardiocytes to 1 mM ouabain resulted in a three-to fourfold increase in al, a2, and a3 mRNA accumulation, and an approximate two-fold increase in fB1 mRNA accumulation. A maximum elevation was reached at 60 min in both cases. The ouabain-induced al mRNA accumulation was still observed in the Ca2"-free culture medium. Exposure of cardiocytes to 10 gM monensin in the absence of extracellular Ca2" also resulted in a threefold increase in al mRNA accumulation. The increased al mRNA expression by 1 mM ouabain was associated with a fourfold increase in al subunit protein accumulation. Transfection experiments with chimeric plasmids containing 5'-flanking sequences of al, a2, and a3 isoform genes and a luciferase reporter gene revealed that 1 mM ouabain caused a twofold increase in luciferase activity in each a system. These results suggest that Na+ directly regulates NaK-ATPase gene expression in cardiocytes. The transfection study further supports the premise that Na+-responsive elements are located within the 5'-flanking sequences of each a isoform gene. (J.