No 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 At 10 weeks of age, the mean labeling index in the ear arteries of 11 rabbits was 0.12% (unpublished results).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...

We studied the tissue weight, dimensions, contractility, elasticity, and sensitivity to exogenous norepinephrine (NE) of denervated and innervated segments of the central ear arteries of white New Zealand rabbits. Three different age groups received unilateral superior cervical ganglionectomies, "growing" at 3-4 weeks, "young adult" at 9-11 weeks, and "mature" at 16-20 weeks. In the growing group, 8 weeks after ganglionectomy, the denervated arteries showed mean decreases in tissue weight (11%), total wall thickness (12+), cross-sectional area of media (17%), contractility (16%), and increases in the tangential modulus of elasticity and sensitivity to NE (2.3-fold) compared to the contralateral control vessels. The change in medial cross-sectional area was significant in the growing and young adult but not the mature animals. The other changes, however, although consistently seen, differed quantitatively among the groups. These results indicate that an intact innervation is necessary for normal development and maintenance of the artery wall. However, the precise consequences of this influence vary at different ages. Whether this influence involves a special trophic factor is not known.

Following partial constriction of the abdominal aorta, the increase in arterial pressure in vessels proximal to the ligature at 3, 6, 14, 21 and 28 days was correlated with pathological changes and with proliferation of cells in the arterial wall measured by ³H-thymidine labeling indices and mitotic counts. The time course of arterial pressure rise and vascular smooth muscle cell proliferation were similar. Patterns of proliferation of cells of the artery wall varied in distribution with time, the presence or absence of traumatic changes seen by light microscopy, and the histological structure of the vessel. Arteries not subject to hypertension did not differ from sham-operated animals.

In the rat and rabbit, evidence for a trophic action of sympathetic nerves on vascular pattern and structure has been reviewed. Effects have been identified by denervation and reinnervation techniques in blood vessels of different size from different regions. Following denervation, increased nonspecific sensitivity to constrictor agents occurs at all ages. In contrast, sympathetic trophic effects on muscle mass, extracellular artery components, and vessel number in the microvasculature were observed predominantly during growth. The mechanism of this action is not known, but the central ear artery in the rabbit was associated with nerve impulses.