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The age-related dynamics of the activity of signalling pathways coupled to alpha1-adrenergic receptors and their dependence on the sympathetic innervation of arterial smooth muscle have been studied. The effects of the protein kinase C inhibitor (GF109203X, 10(-6) M) and the Rho-kinase inhibitor (Y27632, 10(-5) M) on the isometric contraction of the rat saphenous artery, induced by the alpha1-adrenoceptor agonist methoxamine, were examined. It was shown that the sensitivity to methoxamine of arteries from 2-week-old rats that are partially innervated was reduced as compared to adults, but the effects of both inhibitors were more prominent. The denervation induced by the excision of sympathetic ganglia increased the arterial sensitivity to methoxamine but was not accompanied by changes in sensitivity to the inhibitors. Therefore, the postnatal development of the arterial smooth muscle is characterized by a decrease in the contribution of protein kinase C and Rho-kinase to the regulation of contraction; however, these changes do not correlate with changes in the sensitivity of arteries to methoxamine and development of sympathetic innervation.

The characteristics of feeding arteries of diaphragm and medial gastrocnemius (with a diameter of 200-250 micron) were studied. The registration of the mechanical activity of ring preparations under isometric conditions revealed that diaphragm arteries, like arteries of other muscles with a high content of slow muscle fibers, are highly sensitive to adrenoceptor agonists and acetylcholine. The differences in endothelium-dependent relaxation between diaphragm and gastrocnemius arteries are preserved in the presence of L-NAME and diclofenac. Responses to serotonin in diaphragm and gastrocnemius arteries are similar. At the same time, the high density of innervation is characteristic of diaphragm artery only, while in other slow muscles it is low. The density of adrenergic fibers plexus in the diaphragm artery is much higher than in the gastrocnemius artery. The results suggest that the properties of small arteries of diaphragm are determined not only by the oxidative capacity of diaphragm muscle fibers but also by the belonging of the diaphragm to respiratory musculature.

Physical loading raises the sympathetic nervous activity which results in increased minute volume, constriction of peripheral vessels, and elevated blood pressure. These reactions are an outcome of two mechanisms: 1) the central command from cerebral structures that trigger voluntary movements to activate the vasomotor center and 2) the reflexes initiated by mechanic and metabolic changes in a working muscle. The second mechanism of the sympathetic system activation was termed ergoreflex. Ergoreflex controls hemodynamics primarily through activation of mechanosensitive afferents to first of all inhibit the tonic vagal effects on the heart manifested by a leap of heart rate during loading. Activation of chemosensitive afferents comes with some delay in pace with metabolites accumulation in muscles and leads to growth of the efferent sympathetic activity and rise of blood pressure. The metabolic reflex effect is particularly high in the event of muscle fatigue. This review deals with the mechanisms underlying the ergoreflex and their adaptation to hypodynamia, physical loading, and also some pathologies.

Variability of mean arterial pressure (MAP) was examined in chronically instrumented, conscious, freely moving rats with pharmacologically altered efferent sympathetic influences on the cardiovascular system. MAP was recorded for 30 min beat-to-beat, using a computer under both control and experimental conditions: after administration of adrenoceptor antagonists (prazosin or phentolamine) or under P2X receptor inactivation produced either by desensitization with alpha, beta-methylene ATP or by PPADS blockade. Inhibition of adrenergic sympathetic effects on the cardiovascular system produced long-lasting and stable decrease in MAP. Prazosin did not modify MAP variability whereas phentolamine enhanced it. Under P2X receptor desensitization MAP decreased, the hypotensive effect being accompanied by a significant increase in MAP variability. A similar increase in MAP variability was observed after PPADS administration, while MAP level was not changed. Administration of PPADS in combination with phentolamine increased MAP variability more significantly than each of the drugs given separately. Changes in MAP variability under the various experimental conditions were not consistently correlated with changes in heart rate variability. We propose that ATP, being a mediator of sympathetic vasoconstriction, participates in baroreceptor-induced stabilization of MAP level.

With histological technique increased number of sympathetic neurons in cranial ganglia of SHR and Wistar-Kyoto rats in comparison with Wistar line has been shown. The resistance to hypobaric hypoxia (simulated altitude 12000m) was also enhanced in SHR and WKY rats.

The authors analyse the efficacy of sympathetic constrictive effects under the conditions of alternative perfusion. A more intensive vasoconstrictive response in perfusion with a constant discharge was observed in spontaneously hypertensive rats as compared to normotensive ones, and in perfusion with a constant pressure the reverse correlation was noted.

Aim A decrease in the Ca2+ sensitivity of smooth muscle contraction is a hallmark of functional remodelling of blood vessels during development. However, the responsible factors are largely unknown. Here, we tested the hypothesis that the post-natal decline of arterial Ca2+ sensitivity is the result of trophic effects of sympathetic nerves. Methods Contractile responses, intracellular Ca2+ levels and protein expression profiles were compared in saphenous arteries from young (1- and 2-week-old) and adult rats using wire myography, Ca2+ fluorimetry and Western blotting respectively. Results We observed a lower Ca2+ sensitivity of contractions induced by methoxamine, an agonist of α1-adrenoceptors, and U46619, an agonist of thromboxane A2 receptors, in arteries from adult as compared to young animals. Post-natal maturation was associated with stronger expression of regulatory proteins mediating Ca2+-dependent contraction (myosin light chain kinase ( MLCK), myosin targeting subunit ( MYPT1) and h-caldesmon) and weaker expression of proteins regulating Ca2+-independent contraction (Rho kinase, extracellular-regulated kinases ( ERK1/2) and mitogen-activated protein kinases p38 MAPK) in vessels from adult rats. To eliminate the trophic action of sympathetic nerves, we performed lumbar sympathectomy in adult rats. This resulted in higher Ca2+ sensitivity of agonist-induced contractions in denervated as compared to control arteries. Furthermore, denervated arteries contained less MLCK, MYPT1 and h-caldesmon and more ERK1/2 and p38 MAPK. Conclusions Sympathetic denervation reverses developmental changes both in Ca2+ sensitivity and in the expression of regulatory proteins back to the early post-natal phenotype in the rat saphenous artery. We conclude that trophic effects of sympathetic nerves govern functional remodelling of arteries during early post-natal development. [ABSTRACT FROM AUTHOR]