Nitric Oxide Exerts a ‘Direct’ Positive Chronotropic Effect through the Activation of a Novel Signal Trandsuction Pathway in the Sino-Atrial Node

2000 ◽  
Vol 99 (s43) ◽  
pp. 2P-2P
Author(s):  
P Musialek ◽  
L Rigg ◽  
M Lei ◽  
HF Brown ◽  
DA Terrar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronotropic Effect ◽  
Positive Chronotropic Effect

scholarly journals Nitric oxide donors can increase heart rate independent of autonomic activation

1999 ◽  
Vol 87 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Niall Hogan ◽  
Barbara Casadei ◽  
David J. Paterson
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Nervous System ◽  
Autonomic Nervous System ◽  
Sodium Nitroprusside ◽  
Chronotropic Effect ◽  
No Donors ◽  
Autonomic Nervous ◽  
Positive Chronotropic Effect

Administration of nitric oxide (NO) donors in vivo is accompanied by a baroreflex-mediated increase in heart rate (HR). 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 (Δ) in HR (ΔHR, 14 ± 3 beats/min; P < 0.01). This effect was significantly reduced by the I f blocker ZD-7288 (0.2 mg/kg iv; ΔHR, 2 ± 3 beats/min; P = not significant). Similar results were seen with sodium nitroprusside. The positive chronotropic effect of sodium nitroprusside (50 μM) was confirmed in the isolated working rabbit heart preparation (ΔHR, 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.

Possible involvement of nitric oxide-cGMP pathway in the negative chronotropic effect of CD-832, a novel dihydropyridine derivative

Life Sciences ◽  
1998 ◽  
Vol 62 (10) ◽  
pp. 897-903
Author(s):  
K. Noguchi ◽  
T. Shijuku ◽  
C. Nakasone ◽  
K. Takahashi ◽  
S. Higuchi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronotropic Effect ◽  
Negative Chronotropic Effect ◽  
Cgmp Pathway ◽  
Dihydropyridine Derivative

Nitric oxide has no chronotropic effect in right atria isolated from rat heart

1994 ◽  
Vol 255 (1-3) ◽  
pp. 149-156 ◽  
Author(s):  
Richard H. Kennedy ◽  
Kristine K. Hicks ◽  
Johnny E. Brian ◽  
Ernst Seifen
Keyword(s):  
Nitric Oxide ◽  
Rat Heart ◽  
Chronotropic Effect ◽  
Right Atria

scholarly journals Some physiological reactions stimulated by isadrine in experimental hyperthyroidism in rats

1997 ◽  
Vol 43 (4) ◽  
pp. 43-45
Author(s):  
V. I. Sobolev ◽  
Nizar Osman
Keyword(s):  
Latent Period ◽  
Adult Male ◽  
High Reactivity ◽  
Albino Rats ◽  
Chronotropic Effect ◽  
Vapor Mixture ◽  
Experimental Hyperthyroidism ◽  
Physiological Reactions ◽  
Positive Chronotropic Effect

The chronotropic, calorigenic, and thermogenic effects of isopropyl noradrenalin (INA) and of the vapor mixture of INA and propranolol were studied in 86 adult male albino rats over the course of development of hyperthyrosis induced by 1 to 12 injections of triiodothyronin in a dose of 100 \xg/kg. The Pl-adrenergic reaction of the heart and the calorigenic and thermogenic reactions undergo several phases upon stimulation with isadrin in a dose of 2.0 pg/kg/min: latent period, period of high reactivity, and period of reduction of this activity. The efficacy of inderal (25 \ig/kg/min) adrenoblocking of the positive chronotropic effect of exogenously administered isadrin decreases with the progress of hyperthyrosis.

Bradykinin B2-Receptor-Mediated Positive Chronotropic Effect of Bradykinin in Isolated Rat Atria

1998 ◽  
Vol 32 (3) ◽  
pp. 452-456 ◽  
Author(s):  
Qun Li ◽  
Jie Zhang ◽  
Juan F. Loro ◽  
Martin Pfaffendorf ◽  
Pieter A. van Zwieten
Keyword(s):  
Chronotropic Effect ◽  
Bradykinin B2 Receptor ◽  
Rat Atria ◽  
Isolated Rat ◽  
Positive Chronotropic Effect

Effects of endothelin on spontaneous contractions in lymph vessels

1999 ◽  
Vol 277 (2) ◽  
pp. H459-H466 ◽  
Author(s):  
Hiroshi Sakai ◽  
Fumitaka Ikomi ◽  
Toshio Ohhashi
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscles ◽  
Significant Inhibition ◽  
Lymphatic Endothelial Cells ◽  
Chronotropic Effect ◽  
Inotropic Effects ◽  
Mechanical Removal ◽  
Spontaneous Contractions ◽  
Positive Chronotropic Effect ◽  
Stimulation Of

A mode of action of endothelin (ET) on spontaneous contractions was investigated in ring preparations of isolated bovine mesenteric lymphatics. ET-1 at concentrations between 10−10 and 10−9 M caused a dose-dependent increase in the frequency of spontaneous contractions. The specific ETA-receptor antagonist BQ-123 (5 × 10−7 M) caused a significant inhibition of the ET-1-induced positive chronotropic effect in the ring preparations with and without the endothelium. Mechanical denudation of the lymphatic endothelial cells produced a significant potentiation of the ET-induced positive chronotropic effect. BQ-3020 (10−8–10−7M), a selective ETB-receptor agonist, induced dose dependently negative chronotropic and inotropic effects on the spontaneous contractions in the ring preparations with intact endothelium. Mechanical removal of the endothelium caused a significant reduction of the BQ-3020-induced negative chronotropic and inotropic effects. The ET-1-induced positive chronotropic effect was potentiated by pretreatment with N ω-nitro-l-arginine methyl ester (l-NAME) (10−5 M) but unaffected by aspirin (10−5 M). Additional treatment with l-arginine (10−4 M) completely reversed the l-NAME-mediated potentiation of the ET-induced chronotropic effect. These results suggest that stimulation of ETA receptors on the lymphatic smooth muscles causes a positive chronotropic effect on the spontaneous contractions, and stimulation of ETB receptors on the lymphatic endothelial cells induces a release of nitric oxide, which results in the chronotropic and inotropic effects on spontaneous contractions in isolated bovine mesenteric lymphatics.

scholarly journals Metabolic and functional consequences of cytosolic 5′-nucleotidase-IA overexpression in neonatal rat cardiomyocytes

2003 ◽  
Vol 285 (3) ◽  
pp. H991-H998 ◽  
Author(s):  
Graciela B. Sala-Newby ◽  
Nicola V. E. Freeman ◽  
Maria A. Curto ◽  
Andrew C. Newby
Keyword(s):  
Neonatal Rat ◽  
Nucleoside Transporter ◽  
Chronotropic Effect ◽  
Rat Cardiomyocytes ◽  
Adenosine Receptor Antagonist ◽  
Neonatal Rat Cardiomyocytes ◽  
Functional Consequences ◽  
Chronotropic Effects ◽  
Simulated Hypoxia ◽  
Positive Chronotropic Effect

Adenosine exerts a spectrum of energy-preserving actions on the heart negative chronotropic effects. The pathways leading to adenosine formation have remained controversial. In particular, although cytosolic 5′-nucleotidases can catalyze adenosine formation in cardiomyocytes, their contribution to the actions of adenosine has not been documented previously. We recently cloned two closely related AMP-preferring cytosolic 5′-nucleotidases (cN-IA and -IB); the A form predominates in the heart. In this study, we overexpressed pigeon cN-IA in neonatal rat cardiomyocytes using an adenovirus. cN-IA overexpression increased adenosine formation and release into the medium caused by simulated hypoxia and by isoproterenol in the absence and presence of inhibitors of adenosine metabolism. Adenosine release was not affected by an ecto-5′-nucleotidase inhibitor, α,β-methylene-ADP, but was affected by a nucleoside transporter, dipyridamole. The positive chronotropic effect of isoproterenol (130 ±3 vs. 100 ±4 beats/min) was inhibited (107 ±3 vs. 94 ±3 beats/min) in cells overexpressing cN-IA, and this was reversed by the addition of the adenosine receptor antagonist 8-( p-sulfophenyl)theophilline (120 ± 3 vs. 90 ± 4 beats/min). Our results demonstrate that overexpressed cN-IA can be sufficiently active in cardiomyocytes to generate physiologically effective concentrations of adenosine at its receptors.

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