Development Of Sympathetic Innervation Research Articles

The contribution of protein kinase C and rho-kinase to the regulation of receptor-dependent contraction of arteries decreases with age independently of sympathetic innervation

The age-related dynamics of the activity of signaling pathways coupled with α1-adrenoreceptors and their dependence on sympathetic innervation of arterial smooth muscle has been studied. For this purpose, the effects of protein kinase C inhibitor (GF 109203X, 10−6 M and Rho-kinase inhibitor (Y27632, 10−5 M) on isometric contraction of the rat saphenous artery in response to the α1-adrenoreceptor agonist methoxamine were determined. The rats in the age of two weeks (with partially developed sympathetic innervation) had the lower vascular sensitivity to methoxamine than adult rats, but the effects of both inhibitors were more prominent. The denervation induced by excision of sympathetic ganglia in adult rats increased the arterial sensitivity to methoxamine but the sensitivity to inhibitors was unchanged. Thus, the postnatal development of the arterial smooth muscle is accompanied by diminution of the role of protein kinase C and Rho-kinase in the regulation of contraction, but these changes do not correlate with the changes in arterial sensitivity to α1-adrenergic stimulation and development of sympathetic innervation.

1215 Development of sympathetic innervation to the cerebral arterial system in rats as revealed by anterograde labeling with WGA-HRP

1215 Development of sympathetic innervation to the cerebral arterial system in rats as revealed by anterograde labeling with WGA-HRP

Beta adrenergic modulation of cardiac rhythm in a rat model of altered sympathetic neural development

We previously have shown that treatment of neonatal rats (days 1–10) with Nerve Growth Factor (NGF) or its antibody (Ab) modifies α-adrenergic receptor-effector coupling, such that innervated hearts at day 10 show high levels of a 41 kDa GTP regulatory protein (G protein) that is a substrate for pertussis toxin and that links the α 1-receptor to the Na K pump. This receptor-effector pathway results in α adrenergic-induced decreases in automaticity. In contrast, non-innervated hearts at day 10 show lower levels of the pertussis toxin sensitive G-protein and increases in automaticity induced by α-agonist. We now report the effects of administration of NGF, Ab or placebo on β-adrenergic receptor-effector coupling in neonatal rats. Rats were administered NGF, Ab or placebo on days 1–10 of life. On day 10, the β-receptor number and affinity and the stimulatory G-protein, G s, were equivalent across groups. Moreover, the ventricular automatic response to β-adrenergic receptor stimulation was equivalent across groups suggesting there was no change in receptor-effector coupling as a result of the difference in innervation. These results on β-adrenergic receptor-effector coupling considered in light of our prior studies on α-adrenergic coupling suggest that the development of sympathetic innervation is more a determinant of α than β adrenergic modulation of ventricular rhythm.

Hypernoradrenergic Innervation and Vascular Smooth Muscle Hyperplastic Change

Two distinguishing features of the vasculature of the spontaneously hypertensive rat (SHR) are an increased sympathetic innervation and vascular smooth muscle hyperplasia. Evidence supporting the existence of hypernoradrenergic innervation and vascular smooth muscle cell hyperplasia is presented with emphasis upon the possible interrelationships between the two events. The results of experiments designed to explore this relationship are presented and include the determination of the role of endogenous nerve growth factor (NGF) and the influence of exogenous NGF on the development of sympathetic innervation of blood vessels and blood pressure change. Attention is focused upon elevated levels of 3-methylhistidine (a biochemical marker for contractile proteins) in the mesenteric vasculature of the SHR. The potential relationships between hypernoradrenergic innervation and increased concentrations of 3-methylhistidine are explored.

Developmental expression of dystrophin on the rat myocardial cell membrane

The Duchenne muscular dystrophy gene product, dystrophin, is expressed on the cell membrane of skeletal and cardiac muscles. We examined the developmental time course of dystrophin expression in the rat ventricular myocardium. Dystrophin was immunohistochemically undetectable on the 15th embryonic day, but a small amount was expressed on the cell membrane on the 17th embryonic day. The amount increased during the perinatal period reaching adult level at 2 weeks after birth. These findings were supported by immunoblot analysis. Chemical sympathectomy in newborn rats by 6-hydroxydopamine (prevention of innervation) had no detectable influence on myocardial dystrophin expression at 2 weeks after birth. Our results show that dystrophin lining on the rat myocardial cell membrane increases during the perinatal period, and that this process is little influenced by the development of sympathetic innervation.

Role of a pertussis toxin-sensitive protein in the modulation of canine Purkinje fiber automaticity.

We previously have shown that alpha-adrenergic stimulation of canine Purkinje fibers and rat ventricle decreases automaticity. Experiments on rat ventricular myocytes in tissue culture have suggested that the decrease in automaticity induced by alpha-adrenergic stimulation depends on the development of sympathetic innervation and the presence of a pertussis toxin-sensitive, 41-kDa guanosine triphosphate (GTP)-regulatory protein. In the present study, microelectrode and biochemical techniques were used to test the role of the pertussis toxin-sensitive protein and sympathetic innervation in modulating automaticity of adult canine Purkinje fibers. Fibers were incubated in Tyrode's solution alone or in Tyrode's solution plus pertussis toxin (0.1-0.5 microgram/ml) for 24 hours and were then superfused with phenylephrine. Phenylephrine in the 5 x 10(-9)-5 x 10(-8) M range induced a decrease in automaticity in 63% of the 16 fibers not treated with pertussis toxin and an increase in automaticity in 37%. The former group had a higher level of pertussis toxin-sensitive substrate by the [32P]nicotinamide adenine dinucleotide adenosine diphosphate (ADP)-ribosylation assay than the latter. In contrast, all fibers treated with pertussis toxin (0.5 microgram/ml) showed increased automaticity in response to phenylephrine and had no detectable pertussis toxin-sensitive substrate. Over the range of pertussis toxin concentrations studied, there was a smooth concentration-response relation between the substrate levels measured and the automatic response to phenylephrine. As ADP-ribosylatable substrate levels decreased, the percent of fibers showing an increase in automaticity increased.(ABSTRACT TRUNCATED AT 250 WORDS)

The correlation between the development of sympathetic innervation and the development of medial hypertrophy in jejunal arteries in normotensive and spontaneously hypertensive rats

The catecholaminergic innervation of jejunal arteries was examined during development in normotensive and hypertensive rats. It was determined that a hyperinnervation of jejunal vessels in the hypertensive rats is present from 2 weeks of age onwards, before significant elevation of blood pressure and medial hypertrophy of jejunal arteries occurs. It is concluded that this hyperinnervation may be causally related to the medial hypertrophy in arteries of hypertensive animals.

Developing innervation of the chick heart: a histofluorescence and light microscopic study of sympthetic innervation.

The available descriptions of the development of sympathetic innervation of the chick heart conflict with the known sympathetic innervation of the adult chicken heart. The adult heart is innervated by bilateral sympathetic cardiac nerves originating from the first thoracic sympathetic ganglia. These nerves travel lateral and anterior to the lung and join the vagi just before entering the pericardium along the great vessels. Using catecholamine histofluorescence techniques and silver preparations, we have observed the development of the sympathetic cardiac nerves. The sympathetic cardiac nerves arise from the first thoracic sympathetic ganglia on the 7th day of incubation. They grow lateral and then ventral to the developing lungs to join the vagi, and are found in the bulbar region of the heart and atrium on the 10th day of incubation. FLuorescent cells without processes mark the course of the sympathetic cardiac nerves and are present in the bulbar region on the 10th day and thereafter. Sympathetic ganglion cells lose their fluorescence between day 8 and day 16 of incubation. This is presumably due to dilution of the transmitter in the rapidly increasing volume of cytoplasm in the sprouting neurons. Small intensely fluorescent (SIF) and adrenal medullary cells do not undergo a diminution of fluorescence during this period. SIF cells appear well differentiated at 16 days.

The development of sympathetic innervation and the functional state of the cardiovascular system in newborn dogs.

The present study in dogs indicates that the peripheral sympathetic fibers develop mostly after birth and reach a full maturity at about 2 months of life. The norepinephrine content of the heart, spleen, intestine, salivary glands, and adrenal glands increased from birth to 56 days of age. In contrast, the content of the stellate ganglia decreased during this period. In most of the organs studied, the uptake of [3H] norepinephrine developed in parallel with the norepinephrine content, except in the right atrium and salivary glands where it was fully developed soon after birth. During development, the systemic blood pressure increased from 40 to 100 mm Hg. Bilateral adrenal vessel clamping failed to induce a fall in blood pressure in growing dogs which indicates that the adrenal medulla or the baroreceptors did not fully compensate for the lack of peripheral sympathetic fibers and for the lower blood pressure in newborn animals. Although cardiac norepinephrine content was still very low in 10-day-old animals, cardiovascular responses to direct and reflex sympathetic stimulation were similar to those observed in 56-day-old animals. These results indicate that the sympathetic nervous system becomes functional before the fibers reach their full maturity.