Sympathetic Nerve Development in the Rat and Guinea-Pig Heart

Lipp, J. A.; Rudolph, Abraham M.

doi:10.1159/000240497

Cited by 67 publications

(22 citation statements)

References 2 publications

(2 reference statements)

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“…Although it has been suggested that these changes were caused by prejunctional mechanisms (Mackenzie & Standen, 1980), we have observed in the right atria and in the ventricle that sensitivity to Iso decreased in parallel to the sensitivity to NA during development Tanaka et al, 1988a,b), and concluded that the changes were mainly postjunctional in nature. This decrease in sensitivity correlates well with the increase in sympathetic innervation in each region, as determined by examining responsiveness to tyramine Tanaka et al, 1988a,b), NA content (Iversen et al, 1967;Mirkin, 1972), intensity of the fluorescence of catecholamine containing fibres (De Champlain et al, 1970;Lipp & Rudolph, 1972), capacity for NA uptake and retention (Iversen et al, 1967) and by morphological observations (Gomez, 1958).…”

Section: Discussionmentioning

confidence: 75%

Role of β‐adrenoceptor‐adenylate cyclase system in the developmental decrease in sensitivity to isoprenaline in foetal and neonatal rat heart

Tanaka¹,

Shigenobu²

1990

British J Pharmacology

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1 The inotropic and chronotropic sensitivity to noradrenaline and isoprenaline (Iso) of foetal and ngonatal rat heart decreases as the heart becomes sympathetically innervated. In the present study, we have examined adenylate cyclase (AC) activation and fl-adrenoceptor binding to determine whether a developmental decrease in sensitivity was demonstrable in the fl-receptor-AC system of atrial and ventricular membranes from the 15 day foetus and 1 day and 7 day neonates. 2 While the maximum activation of AC by Iso increased with age, the sensitivity expressed in terms of pD2 values decreased from the 15th foetal day to the first day after birth in the atria, and from the first day to the 7th day after birth in the ventricle. 3 In contrast, activation of AC by forskolin was almost identical at all ages both in atria and ventricle. 4 The maximum equilibrium binding of [3H]-dihydroalprenolol decreased with age, the dissociation constant being about the same at all ages in both the atria and ventricle. 5 In conclusion, we have demonstrated a developmental decrease in the sensitivity of AC to Iso in myocardial membrane fractions consistent with the developmental decrease in chronotropic and inotropic sensitivity to fl-adrenoceptor agonists. Although a reduction in ,B-adrenoceptor number partly accounts for the decrease in sensitivity, some other factors such as decreased coupling to AC may largely be responsible.

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Section: Discussionmentioning

confidence: 75%

Role of β‐adrenoceptor‐adenylate cyclase system in the developmental decrease in sensitivity to isoprenaline in foetal and neonatal rat heart

Tanaka¹,

Shigenobu²

1990

British J Pharmacology

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“…Growth cones begin to emerge from the ganglia at approximately embryonic day 18 (E18) and innervate the myocardium and precapillary arterioles during the first three postnatal weeks [postnatal day 0 (P0) through P22] (Berthoud and Powley, 1996). Innervation of the heart starts with the right atrium (P2), followed by the right ventricle (P4), blood vessels (P8), and the left ventricle (P22) (Iversen et al, 1967;Lipp and Rudolph, 1972;Nyquist-Battie et al, 1994).…”

Section: Abstract: Integrins; Vascular Cell Adhesion Molecule-1; Symmentioning

confidence: 99%

α4 Integrins and Vascular Cell Adhesion Molecule-1 Play a Role in Sympathetic Innervation of the Heart

et al. 2002

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Sympathetic neurons innervate the heart early in postnatal development, an event that is crucial for proper modulation of blood pressure and cardiac function. However, the axon guidance cues that direct sympathetic neurons to the heart, and the neuronal receptors that recognize those cues, are poorly understood. Here we present evidence that interactions between the ␣4␤1 integrin on sympathetic neurons and vascular cell adhesion molecule-1 (VCAM-1) in the heart plays a role in cardiac innervation.The ␣4 subunit was detected on postnatal rat superior cervical ganglion (SCG) neurons in culture and in cryosections of SCG and heart. VCAM-1 immunoreactivity was detected on cardiac myocytes that associate with invading sympathetic neurons. Purified recombinant soluble VCAM-1 (rsVCAM-1) stimulated SCG neurite outgrowth at levels comparable with laminin 2/4 and fibronectin (Fn), and outgrowth on rs-VCAM-1 and Fn was blocked by antibodies specific for the ␣4 and ␤1 integrin subunits. Intrathoracic injection of function-blocking antibodies to ␣4 and VCAM-1, as well as a small molecule inhibitor of ␣4 integrins, significantly reduced sympathetic innervation of the heart. These results indicate that the interaction between ␣4 integrin and VCAM-1 is important for sympathetic innervation of the heart.

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“…In the human fetus functional sympathetic and parasympathetic innervation begins prior to birth but remains immature at birth com pared to the adult [2], Thus, the newborn heart displays a limited interaction of the sympathetic and parasympathetic nervous system because of immaturity of both branches of the autonomic nervous system. The developing rat heart provides a good model to study the changes associated with innervation since sympathetic innervation occurs after birth [4] with the earliest func tional connections occurring during the end of the first week of life [5]. Parasympathetic innervation also becomes functionally mature after birth, occurring at the end of the second postnatal week in the rat [6], While the neural limb of both the parasympathetic system and sympathetic system is immature in the new born rat heart, the humoral limb of the sym pathetic system is quite functional with circu lating catecholamines and functional myocar dial (3-adrenoceptors.…”

Section: Introductionmentioning

confidence: 99%

Ontogeny of Rat Myocardial A<sub>1</sub> Adenosine Receptors

Cothran

Lloyd²,

Taylor

et al. 1995

Neonatology

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Adenosine functions as a counterregulatory hormone in the myocardium by decreasing work and thereby protecting the myocardium against ischemia. Functional adenosine A₁ receptors could serve as an important regulatory system in the developing preinnervated heart by balancing the humoral sympathetic input to the heart. The aims of this study were to determine if A₁ adenosine receptors were functionally coupled to their G_i protein in the immature preinnervated heart and to determine if A₁ adenosine receptors were present in greater numbers in the immature heart. One- to 3-day-old rat ventricular cardiomyocyte cultures were exposed to (1) control conditions; (2) isoproterenol, a β-receptor agonist; (3) R-PIA, an A₁ agonist, or (4) isoproterenol and R-PIA. cAMP levels were determined by RIA in each group. Adenosine A₁ receptor density and the equilibrium dissociation constant were determined by binding of an adenosine At receptor antagonist in newborn, 1-week-old, 2-week-old, and adult rat hearts. A₁ stimulation decreased the isoproterenol-induced increase in cAMP by 30%, demonstrating functional A₁ receptors in immature preinnervated myocytes. The A₁ receptor density in the newborn age group was twice the adult and 2-week-old level. We conclude that A₁ receptors in the immature heart are functionally coupled to their effector and that A₁ receptors are present in greater numbers in the immature heart.

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Sympathetic Nerve Development in the Rat and Guinea-Pig Heart

Cited by 67 publications

References 2 publications

Role of β‐adrenoceptor‐adenylate cyclase system in the developmental decrease in sensitivity to isoprenaline in foetal and neonatal rat heart

Role of β‐adrenoceptor‐adenylate cyclase system in the developmental decrease in sensitivity to isoprenaline in foetal and neonatal rat heart

α4 Integrins and Vascular Cell Adhesion Molecule-1 Play a Role in Sympathetic Innervation of the Heart

Ontogeny of Rat Myocardial A<sub>1</sub> Adenosine Receptors

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