Nitric oxide donors can increase heart rate independent of autonomic activation

被引:38
作者
Hogan, N
Casadei, B
Paterson, DJ
机构
[1] Univ Oxford, Physiol Lab, Oxford OX1 3PT, England
[2] John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England
关键词
sodium nitroprusside; molsidomine; baroreflex; rabbit;
D O I
10.1152/jappl.1999.87.1.97
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Administration of nitric oxide (NO) donors in vivo is accompanied by a baroreflex-mediated increase in heart rate (KR). In vitro, however, NO donors can increase HR directly by stimulating a pathway that involves NO, cGMP, and the hyperpolarization-activated current (I-f). The aim of this study was to assess the functional significance of this pathway in vivo by testing whether NO donors can increase HR in the anesthetized rabbit independent of the autonomic nervous system. New Zealand White rabbits were vagotomized, cardiac sympathectomized, and treated with propranolol (0.3 mg/kg iv). The NO donor molsidomine (0.2 mg/kg iv) caused a progressive increase (Delta) in HR (Delta HR, 14 +/- 3 beats/min; P < 0.01). This effect was significantly reduced by the I-f blocker ZD-7288 (0.2 mg/kg iv; Delta HR, 2 +/- 3 beats/min; P = not significant). Similar results were seen with sodium nitroprusside. The positive chronotropic effect of sodium nitroprusside (50 mu M) was confirmed in the isolated working rabbit heart preparation (Delta HR, 17 +/- 3 beats/min; P < 0.01). In conclusion, NO donors exert a small, but significant, positive chronotropic effect in vivo that is independent of the autonomic nervous system. These results are also consistent with data in sinoatrial node cells that show that NO donors increase HR by stimulating I-f.
引用
收藏
页码:97 / 103
页数:7
相关论文
共 29 条
[11]  
LEVINE TB, 1986, AM J CARDIOL, V58, P1035
[12]   Effects of NO on baroreflex control of heart rate and renal nerve activity in conscious rabbits [J].
Liu, JL ;
Murakami, H ;
Zucker, IH .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1996, 270 (06) :R1361-R1370
[13]   EFFECTS OF NITROGLYCERIN ON RELEASE, SYNTHESIS AND METABOLISM OF NOREPINEPHRINE AND ACTIVATION OF TYROSINE-HYDROXYLASE IN GUINEA-PIGS [J].
MA, SX ;
LONG, JP .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 199 (01) :27-33
[14]   ICI-D7288, A NOVEL SINOATRIAL NODE MODULATOR [J].
MARSHALL, PW ;
ROUSE, W ;
BRIGGS, I ;
HARGREAVES, RB ;
MILLS, SD ;
MCLOUGHLIN, BJ .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1993, 21 (06) :902-906
[15]   MODULATION OF BARORECEPTOR ACTIVITY BY NITRIC-OXIDE AND S-NITROSOCYSTEINE [J].
MATSUDA, T ;
BATES, JN ;
LEWIS, SJ ;
ABBOUD, FM ;
CHAPLEAU, MW .
CIRCULATION RESEARCH, 1995, 76 (03) :426-433
[16]   RELATIONSHIP BETWEEN PHARMACOKINETICS AND PHARMACODYNAMICS OF MOLSIDOMINE AND ITS METABOLITES IN HUMANS [J].
MEINERTZ, T ;
BRANDSTATTER, A ;
TRENK, D ;
JAHNCHEN, E ;
OSTROWSKI, J ;
GARTNER, W .
AMERICAN HEART JOURNAL, 1985, 109 (03) :644-648
[17]   THE ROLE OF NITRIC-OXIDE IN THE BARORECEPTOR-CARDIAC REFLEX IN CONSCIOUS WISTAR RATS [J].
MINAMI, N ;
IMAI, Y ;
HASHIMOTO, JI ;
ABE, K .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1995, 269 (03) :H851-H855
[18]   PREVENTION OF VENTRICULAR-FIBRILLATION BY METOPROLOL IN A PIG MODEL OF ACUTE MYOCARDIAL-ISCHEMIA - ABSENCE OF A MAJOR ARRHYTHMOGENIC ROLE FOR CYCLIC-AMP [J].
MULLER, CA ;
OPIE, LH ;
HAMM, CW ;
PEISACH, M ;
GIHWALA, D ;
STEYN, JM ;
BASSET, HM .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1986, 18 (04) :375-387
[19]   Nitric oxide can increase heart rate by stimulating the hyperpolarization-activated inward current, I-f [J].
Musialek, P ;
Lei, M ;
Brown, HF ;
Paterson, DJ ;
Casadei, B .
CIRCULATION RESEARCH, 1997, 81 (01) :60-68
[20]  
Musialek P, 1997, J PHYSIOL-LONDON, V504P, pP83