The effect of purinergic P2 receptor blockade on skeletal muscle exercise hyperemia in miniature swine

2014 ◽  
Vol 114 (10) ◽  
pp. 2147-2155 ◽  
Author(s):  
S. P. Mortensen ◽  
R. M. McAllister ◽  
H. T. Yang ◽  
Y. Hellsten ◽  
M. H. Laughlin
1980 ◽  
Vol 238 (2) ◽  
pp. H191-H195 ◽  
Author(s):  
E. W. Young ◽  
H. V. Sparks

The possibility that prostaglandins (PG) contribute to skeletal muscle exercise hyperemia was tested by blocking PG synthesis with indomethacin and by measuring muscle prostaglandin E (PGE) release. The anterior calf muscles of anesthetized dogs were stimulated at frequencies of 1 Hz, 3 Hz, and 6 Hz under conditions of free flow both before and after indomethacin (5 mg/kg). PGE release was elevated from 14.2 +/- 2.4 to 21.8 +/- 3.4 ng . min-1 . 100 g-1 (P less than 0.01) during stimulation at 3 Hz and from 17.5 +/- 5.1 to 39.2 +/- 9.8 ng . min-1 . 100 g-1 (P less than 0.05) during stimulation of 6 Hz. During exercise at 1 Hz, PGE release was not increased. Indomethacin blocked PGE release and the vascular response to arachidonic acid, but caused essentially no changes in blood flow, oxygen consumption, and vascular conductance during exercise at each frequency. Thus, although PGE release is increased during free flow exercise, inhibiting PG synthesis does not alter exercise hyperemia. However, resting vascular conductance is significantly decreased by indomethacin.


1982 ◽  
Vol 242 (6) ◽  
pp. H949-H954 ◽  
Author(s):  
D. E. Mohrman

Hyperkalemia, hyperosmolality, and hypoxia are known to have synergistic vasodilatory effects on resting skeletal muscle. The purpose of this study was to determine the importance of hyperkalemia and hyperosmolality in the hyperemia accompanying steady-state muscle exercise. Denervated dog gastrocnemius-plantaris muscles were perfused at constant pressure. Blood flow (Q), oxygen consumption (VO2), and venous potassium ion concentration ([K+]), osmolarity (OSM), and oxygen tension (PO2) were measured during steady-state exercise at rates between rest and 6 Hz. In control experiments the transition from rest to 6-Hz exercise resulted in large increases in VO2 and Q but modest increases in venous [K+] (+0.7 +/- 0.2 meq/l) and OSM (+6.1 +/- 1.2 mosmol/kg). Increasing venous [K+] by 2.3 meq/l by intra-arterial infusion of isotonic KCl had no steady-state effect on resting Q, nor did it alter the relationship of Q to VO2 or PO2 during exercise. Similarly, increasing venous OSM by 13 mosmol/kg by hypertonic saline infusion produced no alterations in steady-state exercise hyperemia. These findings indicate that neither local hyperkalemia nor hyperosmolality plays a significant role in sustaining the hyperemia of steady-state exercise.


2007 ◽  
Vol 103 (6) ◽  
pp. 2042-2048 ◽  
Author(s):  
Ilkka Heinonen ◽  
Sergey V. Nesterov ◽  
Jukka Kemppainen ◽  
Pirjo Nuutila ◽  
Juhani Knuuti ◽  
...  

Evidence from both animal and human studies suggests that adenosine plays a role in the regulation of exercise hyperemia in skeletal muscle. We tested whether adenosine also plays a role in the regulation of blood flow (BF) distribution and heterogeneity among and within quadriceps femoris (QF) muscles during exercise, measured using positron emission tomography. In six healthy young women, BF was measured at rest and then during three incremental low and moderate intermittent isometric one-legged knee-extension exercise intensities without and with theophylline-induced nonselective adenosine receptor blockade. BF heterogeneity within muscles was calculated from 16-mm3 voxels in BF images and heterogeneity among the muscles from the mean values of the four QF compartments. Mean BF in the whole QF and its four parts increased, and heterogeneity decreased with workload both without and with theophylline ( P < 0.001). Adenosine receptor blockade did not have any effect on mean bulk BF or BF heterogeneity among the QF muscles, yet blockade increased within-muscle BF heterogeneity in all four QF muscles ( P = 0.03). Taken together, these results show that BF becomes less heterogeneous with increasing exercise intensity in the QF muscle group. Adenosine seems to play a role in muscle BF heterogeneity even in the absence of changes in bulk BF at low and moderate one-leg intermittent isometric exercise intensities.


2018 ◽  
Vol 43 (3) ◽  
pp. 312-315
Author(s):  
Naoto Fujii ◽  
Robert D. Meade ◽  
Jeffrey C. Louie ◽  
Pegah Akbari ◽  
Pierre Boulay ◽  
...  

We assessed the role of purinergic P2 receptors in the regulation of cutaneous vasodilation in young adults at rest and during intermittent moderate-intensity exercise in the heat (35 °C). P2 receptor blockade augmented resting cutaneous vasodilation but had no influence during and following exercise. This increase was partly diminished by nitric oxide synthase inhibition. These results suggest a functional role of P2 receptors in the regulation of cutaneous vascular tone during ambient heat exposure at rest.


1997 ◽  
Vol 82 (6) ◽  
pp. 1862-1868 ◽  
Author(s):  
Richard M. McAllister ◽  
Brian L. Reiter ◽  
John F. Amann ◽  
M. Harold Laughlin

McAllister, Richard M., Brian L. Reiter, John F. Amann, and M. Harold Laughlin. Skeletal muscle biochemical adaptations to exercise training in miniature swine. J. Appl. Physiol. 82(6): 1862–1868, 1997.—The primary purpose of this study was to test the hypothesis that endurance exercise training induces increased oxidative capacity in porcine skeletal muscle. To test this hypothesis, female miniature swine were either trained by treadmill running 5 days/wk over 16–20 wk (Trn; n = 35) or pen confined (Sed; n = 33). Myocardial hypertrophy, lower heart rates during submaximal stages of a maximal treadmill running test, and increased running time to exhaustion during that test were indicative of training efficacy. A variety of skeletal muscles were sampled and subsequently assayed for the enzymes citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, and lactate dehydrogenase and for antioxidant enzymes. Fiber type composition of a representative muscle was also determined histochemically. The largest increase in CS activity (62%) was found in the gluteus maximus muscle (Sed, 14.7 ± 1.1 μmol ⋅ min−1 ⋅ g−1; Trn, 23.9 ± 1.0; P < 0.0005). Muscles exhibiting increased CS activity, however, were located primarily in the forelimb; ankle and knee extensor and respiratory muscles were unchanged with training. Only two muscles exhibited higher 3-hydroxyacyl-CoA dehydrogenase activity in Trn compared with Sed. Lactate dehydrogenase activity was unchanged with training, as were activities of antioxidant enzymes. Histochemical analysis of the triceps brachii muscle (long head) revealed lower type IIB fiber numbers in Trn (Sed, 42 ± 6%; Trn, 10 ± 4; P < 0.01) and greater type IID/X fiber numbers (Sed, 11 ± 2; Trn, 22 ± 3; P < 0.025). These findings indicate that porcine skeletal muscle adapts to endurance exercise training in a manner similar to muscle of humans and other animal models, with increased oxidative capacity. Specific muscles exhibiting these adaptations, however, differ between the miniature swine and other species.


1987 ◽  
Vol 252 (6) ◽  
pp. H1192-H1202 ◽  
Author(s):  
J. M. Lash ◽  
H. G. Bohlen

This study evaluated the possibility that during skeletal muscle contractions tissue O2 tension (Po2) around arterioles and venules decreases substantially more than in the middle of the capillary bed and thereby influences functional hyperemia. Periarteriolar [H+] and [K+] were also measured because most large arterioles are in close proximity to venules such that the biochemical status of the periarteriolar tissue could be influenced by a large decrease in O2 availability in the annulet of tissue surrounding the venules. Stimulation frequencies in the range of 2-12 Hz were used to activate the rat spinotrapezius muscle. Periarteriolar and capillary bed Po2, [H+], and [K+] changed during the first few minutes of stimulation but were restored to near resting concentrations as the functional hyperemia developed. However, perivenular Po2 decreased rapidly to approximately 50-60% of the resting gas tension as contractions began, and only minor recovery occurred. Elevation of tissue and periarteriolar Po2 with an O2-enriched superfusion solution did not prevent dilation during contractions to the same diameter as during the response at very low superfusion Po2. Therefore, the extent to which O2 influences arteriolar dilation and exercise hyperemia in the spinotrapezius muscle of the rat may depend less on periarteriolar and capillary bed Po2 than on the release of vasoactive materials from the nearby perivenular tissues as the availability of O2 decreases.


F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1087 ◽  
Author(s):  
James A. Timmons ◽  
Iain J. Gallagher

The purpose of an F1000 review is to reflect on the bigger picture, exploring controversies and new concepts as well as providing opinion as to what is limiting progress in a particular field. We reviewed about 200 titles published in 2015 that included reference to ‘skeletal muscle, exercise, and ageing’ with the aim of identifying key articles that help progress our understanding or research capacity while identifying methodological issues which represent, in our opinion, major barriers to progress. Loss of neuromuscular function with chronological age impacts on both health and quality of life. We prioritised articles that studied human skeletal muscle within the context of age or exercise and identified new molecular observations that may explain how muscle responds to exercise or age. An important aspect of this short review is perspective: providing a view on the likely ‘size effect’ of a potential mechanism on physiological capacity or ageing.


2002 ◽  
Vol 93 (6) ◽  
pp. 2112-2121 ◽  
Author(s):  
Gunvor Ahlborg ◽  
Jonas Lindström

Cardiovascular diseases are characterized by insulin resistance and elevated endothelin (ET)-1 levels. Furthermore, ET-1 induces insulin resistance. To elucidate this mechanism, six healthy subjects were studied during a hyperinsulinemic euglycemic clamp during infusion of (the ET-1 precursor) big ET-1 alone or after ETA- or ETB-receptor blockade. Insulin levels rose after big ET-1 with or without the ETB antagonist BQ-788 ( P < 0.05) but were unchanged after the ETA antagonist BQ-123 + big ET-1. Infused glucose divided by insulin fell after big ET-1 with or without BQ-788 ( P < 0.05). Insulin and infused glucose divided by insulin values were normalized by ETA blockade. Mean arterial blood pressure rose during big ET-1 with or without BQ-788 ( P < 0.001) but was unchanged after BQ-123. Skeletal muscle, splanchnic, and renal blood flow responses to big ET-1 were abolished by BQ-123. ET-1 levels rose after big ET-1 ( P< 0.01) in a similar way after BQ-123 or BQ-788, despite higher elimination capacity after ETA blockade. In conclusion, ET-1-induced reduction in insulin sensitivity and clearance as well as splanchnic and renal vasoconstriction are ETA mediated. ETA-receptor stimulation seems to inhibit the conversion of big ET-1 to ET-1.


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