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Notes: 1. Four connexin (Cx) molecules, namely Cx37, Cx40, Cx43 and Cx45, are expressed in the gap junctions that exist within and between the cellular layers of arteries.2. Endothelial cells are well coupled by large gap junctions expressing Cx37, Cx40 and, to a lesser extent, Cx43, whose expression may be more subject to regulation by physical factors.3. Smooth muscle cells are more heterogeneously coupled by gap junctions that are small and rare. The identity of the Cx expressed in the media may vary among different arteries.4. Myoendothelial gap junctions are small and more common in resistance arteries with fewer layers of smooth muscle cells. Given the small size of these gap junctions and the rapid turnover rate of Cxs, homocellular coupling in the media and heterocellular coupling between the cell layers may be subject to more dynamic control than coupling in the endothelium.5. Vascular gap junctions have been implicated in a number of vasomotor responses that may regulate vascular tone and blood pressure. These include the mechanism of action of the vasodilator, endothelium-derived hyperpolarizing factor (EDHF), the myogenic constriction to intramural pressure increase, the spontaneous or agonist-induced vasomotion of arteries and arterioles and the spreading vasodilation and constriction observed in microcirculatory networks.6. Few data are available on Cx expression in the media of resistance arteries during hypertension. Changes in the expression of Cx43 described in the media of the aorta of hypertensive rats vary with the hypertensive model studied and are likely to represent adaptations to structural changes in the vascular wall.7. In contrast, in the endothelium of the caudal and mesenteric arteries of spontaneously hypertensive rats, expression of Cxs is significantly decreased compared with arteries from normotensive rats and this decrease is reversed by inhibitors of the renin–angiotensin system.8. During hypertension, the activity of EDHF is decreased in the mesenteric artery, but this occurs much later than the initial increase in blood pressure and the decrease in endothelial Cxs, suggesting that changes in EDHF may not be causally related to hypertension or to the changes in endothelial Cxs.9. Upregulation of the myogenic response and the incidence of vasomotion has been reported in hypertension. Little is currently known of the effects of hypertension on spreading vasomotor responses.10. Deletion of specific Cxs in genetically modified mice is complicated by neonatal lethality or coordinate regulation and compensatory changes in the remaining Cxs. Nevertheless, mice in which Cx40 has been deleted are hypertensive and spreading vasodilatory responses are significantly impaired.11. Determination of a role for specific Cxs in the control of blood pressure must await the development of animals in which Cx expression can be modulated in a more complex temporal and tissue-specific manner.

Notes: 1. The functional innervation of autonomic target tissues occurs early during development, at a time when both the nerves and post-synaptic target tissues are still differentiating.2. Physiological responses appear soon after the arrival of the first fibres when uptake and release mechanisms within the nerves are already functional. Initial responses differ from those in the mature animal, both in the form and, frequently, in the subtypes of receptors involved.3. Results of a number of studies suggest that the initial expression of neurotransmitter receptors during development is largely independent of neural influences. Changes recorded in neurotransmitter receptor expression during development appear to be similarly independent of neural influences.4. While signal transduction pathways coupling adrenergic neurotransmitter receptors to effector responses appear to develop independently of the nerves, the efficient coupling of muscarinic receptors often requires the action of the neurotransmitter, acetylcholine.5. During the period of synapse formation, the neural plexus continues to expand. While developing varicosities can release the neurotransmitter, the capacity for neurotransmitter retention appears to be restricted. Developmental changes in the neurotransmitters that produce functional responses, while well known in the sweat glands, may also be seen in more subtle forms in other target tissues.6. Ultrastructural studies suggest that close physical associations between the membranes of the release sites of the developing nerves and the target cells may form early during development when physiological responses are still immature. These close associations could enable more specific reciprocal interactions between nerves and target cells involving known and novel growth factors, neuropeptides and cytokines important in shaping the mature synaptic characteristics.

Notes: Summary Autonomic ganglia (paravertebral sympathetic and ciliary) formed functional junctions in tissue culture with heart muscle or with smooth muscle of the iris sphincter pupillae, vas deferens or taenia coli. Stimulation of the ganglia after 3–14 daysin vitro evoked contractions of the smooth muscle and either excitatory or inhibitory responses in the heart muscle. Hyoscine abolished contractile responses of smooth muscle in the iris—sympathetic ganglia, vas deferens—ciliary ganglia and taenia coli—ciliary ganglia combinations, and blocked the inhibitory response in the heart—sympathetic ganglia combination, indicating that in these cases the innervation was cholinergic.

Notes: Summary Irides from 3–5 day old rats have been grown 1–3 mm from superior cervical or lumbar paravertebral sympathetic ganglia in modified Rose chambers. The two muscles of the iris received distinctly different innervation patternsin vitro, and these were similar to those seenin vivo. Varicose, adrenergic fibres were consistently associated with the dilator pupillae rather than with the sphincter pupillae while excitatory, cholinergic junctions developed between the nerve fibres and the muscle cells of the sphincter but not the dilator. There was a lack of specificity shown by the sympathetic neurons during this innervation. Fibres from lumbar ganglia formed plexuses within the dilator similar to those formed by superior cervical fibres, and sympathetic, cholinergic fibres were able to substitute for the normal parasympathetic, cholinergic fibres in the sphincter.

Notes: Summary The ultrastructural appearance of cultured sympathetic nerve cell bodies and axons during guanethidine-induced retraction of axons has been described and correlated with phase contrast microscopic observations. In retracting axons, morphological alterations (notably aggregation of smooth membranous tubules and formation of myeloid whorls) occurred in swellings, which appeared to correspond to varicosities. Intervaricose regions of axons showed no significant changes; the organization of neurotubules and neurofilaments appeared to be normal. Axonal mitochondria were apparently undamaged, except in regions close to their cell bodies. In the cell bodies of sympathetic neurons, the early phase of degeneration was characterized by specific mitochondrial damage accompanied by some loss of free ribosomes and rough endoplasmic reticulum. This was followed by a second phase in the cell bodies in which there was substantial accumulation of myeloid whorls and organelles, including neurotubules and neurofilaments. It is suggested that this accumulation has resulted from transfer of some of the contents of the axons to the cell body as a consequence of axon retraction. The morphological features of these two proposed phases bear striking resemblance to ultrastructural alterations characteristic of the first two phases of degeneration of adrenergic neuronsin vivo after guanethidine treatment. Various possibilities are discussed concerning the mechanism underlying guanethidine-induced axon retraction.