Effect of sympathetic denervation on smooth muscle cell proliferation in the growing rabbit ear artery.

Abstract

The effect of sympathetic denervation on the uptake of 3 H-thymidine ( 3 H-Tdr) into the ear artery of a growing rabbit was studied in vitro and in vivo. Uptake into the right artery was compared with that into the left 2 and 3 weeks after left superior cervical ganglionectomy in 4-week-old rabbits. Denervation was confirmed by the absence of catecholamine fluorescence. The total uptake of 3 H-Tdr was determined by scintillation spectrometry, and its distribution in the artery wall was studied by light microscope autoradiography. The denervated ear artery took up significantly less DNA precursor and exhibited fewer labeled vascular smooth muscle cell nuclei in the tunica media than did the control artery. These findings suggest that sympathetic innervation influences the proliferation of vascular smooth muscle in growing rabbits.• During an investigation of the factors affecting arterial smooth muscle cell proliferation, it became desirable to determine whether the sympathetic nervous system influences cell division and growth of the artery wall in the developing animal. To study the effects of sympathetic denervation on the growing ear artery, a left superior cervical ganglionectomy was performed on 4-week-old rabbits. In immature rabbits, appreciable numbers of arterial smooth muscle cell nuclei are labeled after a single injection (pulse label) of 3 H-thymidine ( 3 H-Tdr), a DNA precursor, and mitotic vascular smooth muscle cells are frequently seen. The labeling index and also the mitotic index of arteries studied slowly declines after the first postnatal week. At 10 weeks of age, the mean labeling index in the ear arteries of 11 rabbits was 0.12% (unpublished results). These results are in agreement with those of Spaet and Lejnieks (1), who found a vascular smooth muscle cell labeling index in mature rabbits of 0.16% after a 7-hour infusion of 3 H-Tdr. The normal mature rabbit appears to have a relatively stable arterial cell population; labeled cells are infrequent (2, 3), and mitotic vascular smooth muscle cells are rare.DNA synthesis and hence proliferative potential in the growing rabbit was assessed by measuring both the ability of normal and denervated ear arteries to take up 3 H-Tdr in vitro 2 and 3 weeks following sympathectomy and the labeling index of vascular smooth muscle cells both in vivo and in 14 vitro.3 H-Tdr is utilized by cells in the DNA synthesis (S) phase and incorporated rapidly into DNA by a sequence of phosphorylation steps (4). It is a more sensitive measure of proliferative activity due to the relative lengths of these phases in the cell cycle. In a brief labeling period, only cells in the S phase will incorporate 3 H-Tdr into nuclear DNA, and the distribution of these cells can be demonstrated by autoradiography.3 H-Tdr uptake was measured by scintillation spectrometry.Denervation resulted in significant reductions in 3 H-Tdr uptake into the artery and in the number of smooth muscle cells synthesizing DNA. This finding suggests that the sympathetic nervous system influen...

Relationship between α1-Adrenergic Receptor-Induced Contraction and Extracellular Signal-Regulated Kinase Activation in the Bovine Inferior Alveolar Artery

“…For example, increased sympathetic innervation (Head, 1991) or exogenous elevation of plasma catecholamines (Stewart et al, 1992) has been associated with vascular smooth muscle hypertrophy in vivo. In addition, sympathetic denervation of blood vessels through mechanical (Bevan, 1975), chemical (Fronek et al, 1978), or immunological (Lee et al, 1987) methods results in decreases in DNA synthesis and cell number. The addition of catecholamines to vascular smooth muscle cell cultures increases DNA (Nakaki et al, 1990) and protein synthesis (Chen et al, 1995;Hu et al, 1999), as well as cell growth (Blase and Boissel, 1993).…”

Increased resistance and impaired maximal vasodilation in normotensive vascular beds of rats with coarctation hypertension.

“…It has been suggested that adrenergic neurons may exert a trophic influence on vascular smooth muscle. 20 Exposure to elevated levels of renin-angiotensin-aldosterone 21 or other humoral factors 22 " might in some way alter the composition of vessel walls to increase wall-to-lumen ratio. Clearly, the influence of such systemic factors must be explored further.…”

Review lecture. Neurotransmitters and trophic factors in the autonomic nervous system.

“…These results could be explained by the release of a trophic substance from sympathetic nerves which acts on adenylate cyclase resulting in the production of cyclic AMP, which promotes differentiation, delaying dedifferentiation and proliferation. Further factors may be involved in the regulation of smooth muscle proliferation in vivo, since Bevan (1975) has shown that sympathetic denervation of the ear aretery in the young rabbit results in a reduction in the number of dividing cells compared with the control side, suggesting that the presence ofnerves enhances proliferation.…”