Yohei Sekiguchi

Nitric oxide modulates sympathetic control of left ventricular contraction in vivo in the dog

Recently, evidence has been presented that nitric oxide (NO) modulates myocardial contraction induced by beta-adrenergic stimulation in vitro and in vivo. In this study, we investigated whether inhibition of the L-arginine NO system augments the positive inotropic response of the left ventricle to direct stimulation of the sympathetic nerves in vivo in the dog. Electrical stimulation was applied to the left stellate ganglion (LSG) for 1 min at submaximal (5 V, 2.5, 5 and 10 Hz) and supramaximal intensities (10 V, 10 Hz) in twelve anesthetized and vagotomized dogs. Next, in the same dogs, N(omega)-nitro L-arginine methylester (L-NAME) was infused into the left anterior descending (LAD) coronary artery, and LSG stimulation repeated using the same protocol. Finally, L-arginine was infused into the LAD artery, and LSG stimulation repeated. We used the maximum of the first derivative of left ventricular pressure (LV max d P/dt) as an index of the myocardial contractility. Plasma epinephrine and norepinephrine concentrations were measured in the coronary sinus at 5 V, 2.5 Hz before and after L-NAME treatment in five of twelve dogs. L-NAME treatment significantly augmented the inotropic response of the left ventricle (percent change in the LV max dP/dt) to LSG submaximal stimulation trains from 164 +/- 13 to.212 +/- 21 (P < 0.03), from 187 +/- 15 to 234 +/- 25 (P < 0.05) and from 220 +/- 19 to 280 +/- 33% (P < 0.05), respectively. This response was reversed by L-arginine treatment. However, the inotropic response to the supramaximal stimulation train did not change after L-NAME and L-arginine treatment. L-NAME significantly increased plasma norepinephrine concentration from 0.69 +/- 0.41 to 1.00 +/- 0.52 ng/ml without changing plasma epinephrine concentration in the coronary sinus. It is concluded that the inhibition of the L-arginine NO system augmented the positive inotropic effect on the left ventricle during sympathetic nerve stimulation in normal dogs in vivo.

Immunohistochemical Analysis of Platelet-derived Growth Factor-B Expression in Myocardial Tissues In Hypertrophic Cardiomyopathy

Intimal and/or medial hyperplasia of intramyocardial small vessels is thought to be one of the causes of myocardial ischemia in hypertrophic cardiomyopathy (HCM). However, the pathogenesis of such vascular lesions in HCM is not yet known. To evaluate the pathogenic role of platelet-derived growth factor (PDGF-B) and basic fibroblast growth factor (b-FGF), which have a potential to induce cellular and molecular changes observed in the vessels in HCM, we examined the expression of these molecules and PDGF receptors in cardiac tissues from six patients with HCM and seven controls using immunohistochemistry. The percentage of PDGF-B positive cells in the myocyte population in HCM was significantly higher than that in controls (52.6 +/- 16.2 (mean +/- SD) vs. 21.6 +/- 9.6, p < 0.01). PDGF-B was also observed in vascular regions in HCM (61.1 +/- 25.5% of arterioles) but not in controls. There were no significant differences in the expression of b-FGF and PDGF receptors in the myocyte and non-myocyte populations and the vascular regions between the HCM and control groups. Our study revealed that the expression of PDGF-B protein was up-regulated in HCM, suggesting the contribution of this molecule to the development of intramyocardial vasculopathy.