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      Exhaustive swimming differentially inhibits P2X 1 receptor- and α 1-adrenoceptor-mediated vasoconstriction in isolated rat arteries

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          Abstract

          Aim:

          To investigate the effects of exhaustive swimming exercise on P2X1 receptor- and α1-adrenoceptor-mediated vasoconstriction of different types of arteries in rats.

          Methods:

          Male Wistar rats were divided into 2 groups: the sedentary control group (SCG) and the exhaustive swimming exercise group (ESEG). The rats in the ESEG were subjected to a swim to exhaustion once a day for 2 weeks. Internal carotid, caudal, pulmonary, mesenteric arteries and aorta were dissected out. Isometric vasoconstrictive responses of the arteries to α,β-methylene ATP (α,β-MeATP) or noradrenaline (NA) were recorded using a polygraph.

          Results:

          The exhaustive swimming exercise did not produce significant change in the EC 50 values of α,β-MeATP or NA in vasoconstrictive response of most of the arteries studied. The exhaustive swimming exercise inhibited the vasoconstrictive responses to P2X1 receptor activation in the internal carotid artery, whereas it reduced the maximal vasoconstrictive responses to α1-adrenoceptor stimulation in the caudal, pulmonary, mesenteric arteries and aorta. The rank order of the reduction of the maximal vasoconstriction was as follows: mesenteric, pulmonary, caudal, aorta.

          Conclusion:

          Exhaustive swimming exercise differentially affects the P2X1 receptor- and α1-adrenoceptor-regulated vasoconstriction in internal carotid artery and peripheral arteries. The ability to preserve purinergic vasoconstriction in the peripheral arteries would be useful to help in maintenance of the basal vascular tone during exhaustive swimming exercise.

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          Most cited references39

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          Regulation of brain function by exercise.

          The effect of excercise on brain function was investigated through animal experiments. Exercise leads to increased serum calcium levels, and the calcium is transported to the brain. This in turn enhances brain dopamine synthesis through a calmodulin-dependent system, and increased dopamine levels regulate various brain functions. There are abnormally low levels of dopamine in the neostriatum and nucleus accumbens of epileptic mice (El mice strain) and spontaneously hypertensive rats (SHR). The low dopamine levels in those animals were improved following intracerebroventricular administration of calcium chloride. Dopamine levels and blood pressure in SHR were also normalized by exercise. In epileptic El mice, convulsions normalized dopamine levels and physiologic function. These findings suggest that exercise or convulsions affect brain function through calcium/calmodulin-dependent dopamine synthesis. This leads to the possibility that some symptoms of Parkinson's disease or senile dementia might be improved by exercise.
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            Cloning OF P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels.

            Two new P2X receptor cDNAs (P2X5 and P2X6) were isolated and expressed. All six proteins are 36-48 percent identical and seem to have two transmembrane segments with a large extracellular loop. Functionally, P2X5 and P2X6 receptors most resemble P2X2 and P2X4; they desensitize only slowly and do not respond to alpha beta methylene-ATP. P2X6 receptors, like P2X4, receptors, are not blocked by the antagonists suramin and pyridoxal-5-phosphate-6-azophenyl-2',4'-disulfonic acid. P2X6 and P2X5 receptors express at lower levels than P2X1-P2X4 receptors do, perhaps indicating that they do not normally form homomultimeric channels. P2X6 and P2X4 are the receptors expressed most heavily in brain, where their RNAs have a widespread and extensively overlapping distribution. The spinal cord expresses all receptors except P2X3. P2X2, P2X4, and P2X6, are the most abundant in the dorsal horn. Sensory neurons of the trigeminal, dorsal root, and nodose ganglia express all six RNAs; P2X3 is found only there. The functional properties and tissue distribution of these six P2X receptors indicate new roles for ATP-gated ion channels.
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              P2 receptors in cardiovascular regulation and disease

              The role of ATP as an extracellular signalling molecule is now well established and evidence is accumulating that ATP and other nucleotides (ADP, UTP and UDP) play important roles in cardiovascular physiology and pathophysiology, acting via P2X (ion channel) and P2Y (G protein-coupled) receptors. In this article we consider the dual role of ATP in regulation of vascular tone, released as a cotransmitter from sympathetic nerves or released in the vascular lumen in response to changes in blood flow and hypoxia. Further, purinergic long-term trophic and inflammatory signalling is described in cell proliferation, differentiation, migration and death in angiogenesis, vascular remodelling, restenosis and atherosclerosis. The effects on haemostasis and cardiac regulation is reviewed. The involvement of ATP in vascular diseases such as thrombosis, hypertension and diabetes will also be discussed, as well as various heart conditions. The purinergic system may be of similar importance as the sympathetic and renin-angiotensin-aldosterone systems in cardiovascular regulation and pathophysiology. The extracellular nucleotides and their cardiovascular P2 receptors are now entering the phase of clinical development.
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                Author and article information

                Journal
                Acta Pharmacol Sin
                Acta Pharmacol. Sin
                Acta Pharmacologica Sinica
                Nature Publishing Group
                1671-4083
                1745-7254
                February 2012
                03 February 2012
                : 33
                : 2
                : 221-229
                Affiliations
                [1 ]Integration of Traditional and Western Medical Research Academy of Hebei Province , Shijiazhuang 050035, China
                [2 ]Department of Pharmacology, Institute of Chinese Integrative Medicine, Hebei Medical University , Shijiazhuang 050017, China
                [3 ]Department of Hand Surgery, The Third Affiliated Hospital of Hebei Medical University , Shijiazhuang 050051, China
                Author notes
                Article
                aps2011148
                10.1038/aps.2011.148
                4010332
                22301861
                e9037c70-aee8-4b19-9d49-5353c5b069fa
                Copyright © 2012 CPS and SIMM
                History
                : 22 January 2011
                : 10 October 2011
                Categories
                Original Article

                Pharmacology & Pharmaceutical medicine
                exhaustive exercise,swimming,α1-adrenoceptor,p2x1 receptor,vasoconstriction,artery

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