Chronotropic effects of nitric oxide in the denervated human heart

被引:24
作者
Chowdhary, S
Harrington, D
Bonser, RS
Coote, JH
Townend, JN
机构
[1] Univ Hosp Birmingham, Dept Cardiovasc Med, Birmingham, W Midlands, England
[2] Univ Hosp Birmingham, Dept Cardiothorac Surg, Birmingham, W Midlands, England
[3] Univ Hosp Birmingham, Dept Physiol, Birmingham, W Midlands, England
[4] Univ Birmingham, Birmingham, W Midlands, England
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2002年 / 541卷 / 02期
关键词
D O I
10.1113/jphysiol.2001.015107
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Nitric oxide synthase is expressed in the sino-atrial node and animal data suggests a direct role for nitric oxide on pacemaker activity. Study of this mechanism in intact humans is complicated by both reflex and direct effects of nitric oxide on cardiac autonomic control. Thus, we have studied the direct effects of nitric oxide on heart rate in human cardiac transplant recipients who possess a denervated donor heart. In nine patients, the chronotropic effects of systemic injection of the nitric oxide synthase inhibitor N-G-monomethyl-L-arginine (L-NMMA) (3 mg kg(-1)) or increasing bolus doses of the nitric oxide donor, sodium nitroprusside (SNP), were studied. Injection Of L-NMMA increased mean arterial pressure by 17 +/- 2 mmHg (mean +/- S.E.M.; P < 0.001) and also had a significant negative chronotropic effect, lengthening the R-R interval by 54 +/- 8 ms (P < 0.001). This bradycardia was not reflex in origin since injection of the non-NO-dependent vasoconstrictor, phenylephrine (100 mug) achieved a similar rise in mean arterial pressure (18 +/- 3 mmHg; P < 0.001) but failed to change R-R interval duration (DeltaR-R = -3 +/- 4 ms). Furthermore, no change in levels of circulating adrenaline was observed with L-NMMA. Conversely, injection of sodium nitroprusside resulted in a positive chronotropic effect with a dose-dependent shortening of R-R interval duration, peak DeltaR-R = -25 +/- 8 ms with 130 mug (P < 0.01). These findings indicate that nitric oxide exerts a tonic, direct, positive chronotropic influence on the denervated human heart. This is consistent with the results of animal experiments showing that nitric oxide exerts a facilitatory influence on pacemaking currents in the sino-atrial node.
引用
收藏
页码:645 / 651
页数:7
相关论文
共 29 条
[1]  
Arrowood JA, 1997, CIRCULATION, V96, P3492
[2]   Effect of sympathetic reinnervation on cardiac performance after heart transplantation. [J].
Bengel, FM ;
Ueberfuhr, P ;
Schiepel, N ;
Nekolla, SG ;
Reichart, B ;
Schwaiger, M .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (10) :731-738
[3]   DEMONSTRABLE CARDIAC REINNERVATION AFTER HUMAN HEART-TRANSPLANTATION BY CAROTID BAROREFLEX MODULATION OF RR INTERVAL [J].
BERNARDI, L ;
BIANCHINI, B ;
SPADACINI, G ;
LEUZZI, S ;
VALLE, F ;
MARCHESI, E ;
PASSINO, C ;
CALCIATI, A ;
VIGANO, M ;
RINALDI, M ;
MARTINELLI, L ;
FINARDI, G ;
SLEIGHT, P .
CIRCULATION, 1995, 92 (10) :2895-2903
[4]   Role of nitric oxide in the regulation of cardiovascular autonomic control [J].
Chowdhary, S ;
Townend, JN .
CLINICAL SCIENCE, 1999, 97 (01) :5-17
[5]   L-arginine augments cardiac vagal control in healthy human subjects [J].
Chowdhary, S ;
Nuttall, SL ;
Coote, JH ;
Townend, JN .
HYPERTENSION, 2002, 39 (01) :51-56
[6]   Nitric oxide and cardiac autonomic control in humans [J].
Chowdhary, S ;
Vaile, JC ;
Fletcher, J ;
Ross, HF ;
Coote, JH ;
Townend, JN .
HYPERTENSION, 2000, 36 (02) :264-269
[7]   Selected Contribution: Axial stretch increases spontaneous pacemaker activity in rabbit isolated sinoatrial node cells [J].
Cooper, PJ ;
Lei, M ;
Cheng, LX ;
Kohl, P .
JOURNAL OF APPLIED PHYSIOLOGY, 2000, 89 (05) :2099-2104
[8]  
FAGARD R, 1995, ACTA CARDIOL, V50, P369
[9]  
Frey A. W., 1996, Clinical Science (London), V91, P146
[10]   Reinnervation of the transplanted human heart as evidenced from heart rate variability studies [J].
Halpert, I ;
Goldberg, AD ;
Levine, AB ;
Levine, B ;
Kornberg, R ;
Kelly, C ;
Lesch, M .
AMERICAN JOURNAL OF CARDIOLOGY, 1996, 77 (02) :180-183