The rapid onset of vasodilatation within seconds of a single contraction suggests that the vasodilators involved may be products of skeletal muscle activation, such as potassium (K + ). To test the hypothesis that K + was in part responsible for the rapid dilatation produced by muscle contraction we stimulated four to five skeletal muscle fibres in the anaesthetized hamster cremaster preparation in situ and measured the change in diameter of arterioles at a site of overlap with the stimulated muscle fibres before and after a single contraction stimulated over a range of stimulus frequencies (4, 10, 20, 30, 40, 60 and 80 Hz; 250 ms train duration). Muscle fibres were stimulated in the absence and presence of an inhibitor of a source of K + , the voltage dependent K + channel inhibitor 3,4-diaminopyridine (DAP, 3 × 10 −4 M) and inhibitors of the K + dilatory signal transduction pathway, either a Na + K + -ATPase inhibitor (ouabain; 10 −4 M) or an inward rectifying K + channel inhibitor (barium chloride, BaCl 2 ; 5 × 10 −5 M). We observed significant inhibitions of the rapid dilatation at all stimulus frequencies with each inhibitor. The dilatory event at 4 s was significantly inhibited at all stimulus frequencies by an average of 65.7 ± 3.6%, 58.8 ± 6.1% and 64.4 ± 2.1% in the presence DAP, ouabain and BaCl 2 , respectively. These levels of inhibition did not correlate with non-specific changes in force generation by skeletal muscle measured in vitro. Therefore, our data support that K + is involved in the rapid dilatation in response to a single muscle contraction across a wide range of stimulus frequencies.

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Dua AK, Dua N, Murrant CL. Skeletal muscle contraction-induced vasodilator complement production is dependent on stimulus and contraction frequency. Am J Physiol Heart Circ Physiol 297: H433-H442, 2009. First published May 22, 2009 doi:10.1152/ajpheart.00216.2009.-To test the hypothesis that the vasodilator complement that produces arteriolar vasodilation during muscle contraction depends on both stimulus and contraction frequency, we stimulated four to five skeletal muscle fibers in the anesthetized hamster cremaster preparation in situ and measured the change in diameter of arterioles at a site of overlap with the stimulated muscle fibers. Diameter was measured before, during, and after 2 min of skeletal muscle contraction stimulated over a range of stimulus frequencies [4,20, and 40 Hz;15 . L-NAME inhibited the dilations at all stimulus frequencies and contraction frequencies except 60 cpm. XAC inhibited the dilations at all contraction frequencies and stimulus frequencies except 40 Hz. Glibenclamide inhibited all dilations at all stimulus and contraction frequencies, and DAP did not inhibit dilations at any stimulus frequencies while attenuating dilation at a contraction frequency of 60 cpm only. Our data show that the complement of dilators responsible for the vasodilations induced by skeletal muscle contraction differed depending on the stimulus and contraction frequency; therefore, both are important determinants of the dilators involved in the processes of arteriolar vasodilation associated with active hyperemia. stimulus frequency; contraction frequency; arteriole; skeletal muscle contraction; active hyperemia BLOOD FLOW TO ACTIVE SKELETAL muscle increases during contraction. It is hypothesized that active skeletal muscle cell metabolites are a source of vasodilators that cause active hyperemia during contraction, but there is little consensus as to the identity of the vasodilators involved. A host of potential metabolic vasodilators such as adenosine (ADO), hydrogen ions, decreased oxygen tension, carbon dioxide, phosphate, etc., as well as a host of endothelial-derived products and products of muscle activation such as nitric oxide (NO), potassium (K ϩ ), prostaglandins, ACh, ATP-dependent K ϩ (K ATP ) channels, etc. (for review, see Refs. 6,18,28,36), have been implicated in the processes of active hyperemia, but there is a general lack of agreement as to the relative importance of each. We have been investigating the impact of stimulation parameters in the processes of arteriolar vasodilation during active hyperemia to understand this general lack of agreement. We surmised that if the dilators are proposed to be products of skeletal muscle activation or metabolism then it stands to reason that if activation or metabolism is changed through different stimulation parameters then the dilators being produced may also change. Thus, to understand the impact that stimulation parameters have on the production of different vasodilators in active hyperemia, we have investigated the effects of stimulation par...

HI-6 is an oxime experimentally developed for reactivation of previously untreatable soman-phosphorylated acetylcholinesterase. It has been shown to be effective in restoring acetylcholinesterase activity after poisoning with other "nerve agents" namely VX and sarin; however, its antidotal qualities for the treatment of organophosphorus pesticide poisoning are not well known. HI-6, and other H-series oximes, apparently act in a number of ways: reactivation of acetylcholinesterase, blockage of ganglia and muscarinic receptors, stimulation of vasopressor and respiratory centre receptors, chemical combination with agents, restoration of neuromuscular transmission, retardation of the formation of the aged inhibitor-enzyme complex, and (or) inhibition of the release of acetylcholine.

Dilated cardiomyopathy (DCM) is an idiopathic condition that results from impaired ventricular systolic function. Thyroid diseases have been known to cause myriad changes in the structure and function of the heart. Diastolic dysfunction is a common abnormality reported in hypothyroidism. However, hypothyroidism-induced DCM and systolic dysfunction is an uncommon phenomenon, especially as the initial presenting manifestation of hypothyroidism. The current article describes the case of a young female who presented with symptoms of heart failure and was diagnosed as having DCM as echocardiography revealed left ventricular global hypokinesia and severely depressed systolic function. Thyroid profile revealed a grossly elevated thyroid-stimulating hormone (TSH) value of 313 μIU/ml; free thyroxine (fT4) was 0.220 ng/dl. The present case presented with DCM as the initial presentation of hypothyroidism and improved significantly after five months of levothyroxine replacement therapy.