Effects of neuropeptide Y on ion channels in ventricular myocytes / 生理学报

Neuropeptide Y (NPY) co-exists with norepinephrine (NE) in sympathetic terminals, and is the most abundant neuropeptide in myocardium. Many studies have focused on the effects of NE on ion channels in cardiac myocytes and its physiological significance has been elucidated relatively profoundly. There have been few investigations, however, on the physiological significance of NPY in myocardium. The effects of NPY on L-type Ca2+ channel currents (I(Ca-L)) were evaluated in some studies and different results were presented, which might be attributed to the different species of animal tested and different methods used. It is necessary, therefore, to study the effects of NPY on ion channels in cardiac myocytes systematically and further to discuss the biological significance of their coexistence with NE in sympathetic terminals. The single ventricular myocytes from adult rat or guinea pig (only for measuring I(K)) were prepared using enzymatic dispersion. I(Ca-L), I(to), I(Na/Ca), I(Na) and I(K) in the cellular membrane were observed using whole cell voltage-clamp recording. In the present study, NPY from 1.0 to 100 nmol/L dose-dependently inhibited I(Ca-L) (P<0.01, n=5). The maximal rate of inhibition in this study reached 39% and IC(50) was 1.86 nmol/L. NPY had no effect on the voltage-dependence of calcium current amplitude and on the voltage-dependence of the steady-state gating variables. I(Ca-L) was activated at -30 mV, reaching the maximum at 0 mV. When both NE and NPY were applied with a concentration ratio of 500:1, 10 nmol/L NPY inhibited I(Ca-L) that had been increased by 5 mumol/L NE, which was consistent with the effect of NPY only on I(Ca-L). NPY also inhibited I(Na/Ca). At a concentration of 10 nmol/L, NPY inhibited inward and outward I(Na/Ca) from (0.27+/-0.11) pA/pF and (0.45+/-0.12) pA/pF to (0.06+/-0.01) pA/pF and (0.27+/-0.09) pA/pF, respectively (P<0.05, n=4). NPY at 10 nmol/L increased I(to) from (12.5+/-0.70) pA/pF to (14.7+/-0.59) pA/pF(P<0.05, n=4). NPY at 10 nmol/L did not affect I(Na) in rat myocytes and I(K) in guinea pig myocytes. NPY increased the speed of action potential depolarization and reduced action potential duration of I(Ca-L), I(Na/Ca) and I(to), which contributed to the reduction of contraction. These results indicate that the effects of NPY are opposite to the effects of NE on ion channels of cardiac myocytes.

Effect of losartan on produce of sera autoantibodies to angiotensin II-1 receptor in renovascular hypertension rats / 中国应用生理学杂志

<p><b>AIM AND METHODS</b>The effects of losartan (after operation 2 week to 10 week, 5 mg/kg d ig) on generation of AT1R-AA in sera were observed during development of hypertension in rats. The renovascular hypertension (RVH) model was established by two-kidney one-clip method, a synthetic peptide corresponding to amino acid sequence 165-191 of the second extracellular loop of the angiotensin II-1 receptor (AT1R) was used as antigen, SA-ELISA were used to examine sera AT1R autoantibody (AT1R-AA).</p><p><b>RESULTS</b>The frequencies and titres of AT1R-AA after operation one week rats were significantly increased (P < 0.05). The treatment with losartan not only inhibited structural and functional changes, but also the frequencies and titres of AT1R-AA was significantly lower (P < 0.05) than RVH group.</p><p><b>CONCLUSION</b>It is suggested that the losartan significantly inhibits generation of the AT1R-AA.</p>