Supersensitivity of the Isolated Rat Heart after Chemical Sympathectomy with 6-Hydroxydopamine

Nadeau, Réginald; Champlain, Jacques de; Tremblay, G

doi:10.1139/y71-005

Cited by 65 publications

(30 citation statements)

References 14 publications

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“…There is experimental evidence to suggest that after denervation return of functional activity precedes complete regrowth of nerve fibers. For example, functional activity of the rat heart, as assessed by the chronotropic response to tyramine, has been shown to approach control levels 2 wk after sympathectomy with 6-OH-dopamine (33). The return of functional activity occurred at a time when myocardial catecholamine stores, which parallel regrowth of nerve fibers, were still 80% depleted.…”

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confidence: 99%

Role of the Renal Sympathetic Nerves in the Development and Maintenance of Hypertension in the Spontaneously Hypertensive Rat

Winternitz¹,

Katholi²,

Oparil³

1980

J. Clin. Invest.

205

114

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A B S T R A C T Neurogenic factors and, in particular, enhanced renal sympathetic tone, have been implicated in the pathogenesis of hypertension in the spontaneously hypertensive rat of the Okamoto strain. To examine the hypothesis that the renal sympathetic nerves contribute to the development and maintenance of hypertension by causing urinary sodium retention, 7-wk-old (early hypertensive) and 18-wk-old (established hypertensive) male spontaneously hypertensive rats were subjected to bilateral renal denervation and compared with sham-operated controls. In 7-wk-old animals renal denervation delayed the onset and slowed the rate of developmentofhypertension. These alterations were associated with a significantly greater fractional excretion of sodium (percentage of sodium intake excreted) during the first 3 wk after denervation. Blood pressure 2 wk after surgery was 169+3.5 (sham) vs. 150+2.4 mm Hg (denervated) (P < 0.001), corresponding to fractional sodium excretions of 65±1.3% (sham) vs. 80+2.3% (denervated) (P < 0.001). By the 5th wk after surgery, at which time an increase in renal norepinephrine content of denervated animals suggested reinnervation, blood pressures in the two groups converged (sham, 199+6.5 mm Hg vs. denervated 180+3.5 mm Hg, NS) and there was no difference in sodium excretion (sham, 77+2.5% vs. denervated 79±2.3%). Plasma and kidney renin activity of denervated animals did not differ significantly from that of sham-operated controls. In 18-wk-old rats renal denervation did not alter blood pressure or urinary sodium excretion. These data indicate that the renal svmpathetic nerves contribute to the development of hypertension in the spontaneously hypertensive rat in Dr. Wintemitz is the recipient of a National Heart, Lung, and Blood Clinical Investigator Award (l-K08 HL00707-01).

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mentioning

confidence: 99%

Role of the Renal Sympathetic Nerves in the Development and Maintenance of Hypertension in the Spontaneously Hypertensive Rat

Winternitz¹,

Katholi²,

Oparil³

1980

J. Clin. Invest.

205

114

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“…6-OHDA was used to cause an effective chemical sympathectomy (37). This was checked by tyramine administration (0.2 mg in a 0.5-ml bolus), which elicited only a minor heart rate increase (3.0 ± 0.8 beats per min; n = 10) in hearts from 6-OHDA-treated rats as compared to controls (32.9 ± 1.2 beats per min; n = 6).…”

Section: Resultsmentioning

confidence: 99%

Neural control of the endocrine rat heart.

Jiao

Baertschi²

1993

Proc. Natl. Acad. Sci. U.S.A.

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Although atrial stretch is the accepted stimulus for atrial natriuretic factor (ANF), in vivo studies suggest a stretch-independent, neurafly induced ANF release mechanism. Thus the hypothesis that cardiac nerves can stimulate ANF secretion was tested in the Langendorff-perfused, paced rat heart. Venom from the scorpion Centruroides sculpturatus was used to activate neuronal sodium channels, veratridine was added to activate sodium channels (predominantly in myocytes), and electrical stimulation was applied to the right atrial appendage. The efficacy of nerve stimulation was verified by measurements of increased neuropeptide Y in the effluent. ANF levels in the effluent increased by 120% over baseline with 0.5 IAM scorpion venom and by 88% with 0.5 ,uM veratridine (P < 0.01). Cardiac mechanics did not explain the large, concentration-dependent ANF response to the scorpion venom, since changes in the left ventricular developed pressure were small, opposite to those induced by veratridine, and unaffected by sympathectomy or adrenergic receptor blockade. Prior chemical sympathectomy and adrenergic receptor blockade almost abolished the ANF response to scorpion venom but hardly affected the ANF response to veratridine. Addition of 1FaM tetrodotoxin abolished all ANF responses. Electrical stimulation of the atrial appendage increased the ANF secretion by 60.2% (P < 0.02), in con,junction with neuropeptide Y, whereas control stimulations were ineffective. These studies unequivocally demonstrate that stimulation of cardiac sympathetic nerves potently stimulates ANF secretion.Atrial natriuretic factor (ANF), a potent natriuretic, diuretic, and vasorelaxant peptide (1), is thought to play an important role in the regulation of blood volume (2, 3). Atrial stretch (4) and blood volume expansion (5) stimulate ANF release, and ANF reduces the blood volume through increased renal excretions, inhibition offluid-retaining hormones, and loss of fluid to the interstitial space (2, 3). Quenching of circulating ANF with anti-ANF antibody reduces the renal response (diuresis) to acute volume expansion (6). However, doubts have been raised about this appealing concept in recent years. Chronic ANF infusions in man and dog have transient effects on renal excretions of salt and water (7,8), challenging the concept that ANF is a blood volume regulatory hormone. ANF is released in the absence of atrial stretch in hypoxic hearts (9), hypoxic animals (10) and humans (11), and in pulmonary hypertension (12,13). Both endothelium-derived compounds (14) and neural factors (13) may be involved in this ANF release.The evidence for a neural regulation of ANF is intriguing, but it has remained indirect and inconclusive. The ANF response to an unphysiological (20 ml/kg of body weight) volume expansion is blunted in pithed rats (15), but pithing inevitably alters baseline parameters (e.g., baseline ANF). Others found that the ANF response to a similar blood volume expansion is unaltered by autonomic denervation orThe publication costs of this...

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“…A chemical denervation of the sympathetic nerve terminals was made by a pretreatment of the animals with reserpine [7][8][9][10][11][12] or 6-OHDA [13][14][15], the former being dissolved in 20% ascorbic acid solution and given intraperitoneally at doses of 2 to 8 mg/kg body weight 24 h before isolation of the heart, and the latter by an intravenous injection at the ear vein at doses of 50 to 100 mg/kg body weight 24 h before isolation or by repeated injections, once a day for 2 days, at a dose of 50 mg/kg body weight. In each isolated heart it was determined that the pretreatments produced complete chemical denervations of the sympathetic nerve terminals, when there was no change in the HR and contraction forces in response to tyramine (Ty) applied to the perfusate.…”

Section: Methodsmentioning

confidence: 99%

“…To clarify whether these inotropic effects of DA as well as the chronotropic ones are direct actions on the cardiac muscles or indirect ones by releasing noradrenaline (NA) from the sympathetic nerve terminals in the cardiac muscles, the sympathetically denervated preparations by the treatments with reserpine [7][8][9][10][11][12] or 6-hydroxydopamine (6-OHDA) [13][14][15] were used, as reported previously. To the author's knowledge, it remains unknown whether the arrhythmogenic effects of DA could be produced by the direct or indirect actions.…”

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confidence: 99%

Inotropic, Chronotropic, and Arrhythmogenic Effects of Dopamine on the Isolated Working Heart of Rabbit

Wakita¹

2007

J. Physiol. Sci

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Some improvements of Kodama's method for perfusing the isolated rabbit heart in its working mode were made. Increases in the right and left atrium pressure, together with an increase in the pulmonary artery pressure, were observed to occur immediately after the start of venous return, and then all of the increased pressures were found to remain at each constant level. In these stable states, the administration of dopamine (DA) into the perfusate was found to produce dose-related increases in contractile activities. In the preparations denervated with reserpine or 6-hydroxydopamine, in which tyramine (Ty) produced no response, the inotropic effectiveness of DA did not differ from that in the normal ones. On the other hand, responses to noradrenaline (NA) were found to increase significantly after the denervation. DA produced a dose-related increase in heart rates in the normal preparation, and this effect was greatly suppressed in the denervated preparations, suggesting that the primary chronotropic effect of DA is an indirect one via the release of NA from the sympathetic nerve terminals. Arrhythmogenic effects of NA, Ty or DA were also observed in these preparations. At all the doses tested, the incidence rates by NA were as high as 50% or more, the type of arrhythmia being recognized as atrial or ventricular extrasystole from the ECG analysis. On the other hand, the rates by DA were relatively low, less than 34%. From a comparison of the incidence rates between the normal and denervated preparations, this effect of DA was considered to be primarily an indirect one.Key words: isolated rabbit heart, perfusion method, inotropic effect of dopamine, chronotropic effect of dopamine, arrhythmogenic effect of dopamine.In regard to the methods for perfusing isolated mammalian heart preparations, Langendorff's is well known and has been used for more than 100 years for cardiovascular research in physiological, biochemical and/or pharmacological aspects [1,2]. In a heart perfused with this method, the retrograde perfusion via the cannulated aorta is designed to produce a constant flow or constant pressure in the aorta with no outflow or only mere outflow from the right or left ventricle, and there is no venous return except for a quite small amount of perfusate drainage via the coronary sinus to the right or left atrium. In this respect, Langendorff's preparation is not working.Kodama in 1961 attempted to convert the isolated rabbit heart preparation into a working mode by constructing an artificial venous and arterial circulation system using silicon and glass tubes and perfusing the heart via the vena cava and pulmonary vein to keep sufficient venous return to the ventricles [3][4][5][6]. In a heart thus perfused with a venous and arterial circulation system that is similar to that in vivo, the simultaneous recordings of perfusate pressures at the various parts of veins and arteries were possible, and it was recognized that the pressure of either the right or left ventricle exceeds that of the pulmonary or ao...

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Supersensitivity of the Isolated Rat Heart after Chemical Sympathectomy with 6-Hydroxydopamine

Cited by 65 publications

References 14 publications

Role of the Renal Sympathetic Nerves in the Development and Maintenance of Hypertension in the Spontaneously Hypertensive Rat

Role of the Renal Sympathetic Nerves in the Development and Maintenance of Hypertension in the Spontaneously Hypertensive Rat

Neural control of the endocrine rat heart.

Inotropic, Chronotropic, and Arrhythmogenic Effects of Dopamine on the Isolated Working Heart of Rabbit

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