Abnormal Membrane Localization of α2 Isoform of Na,K-ATPase in m. soleus of Dysferlin-Deficient Mice.

Dysferlin protein plays a key role in the multimolecular complex responsible for the maintenance of sarcolemma integrity and skeletal muscle cell functioning. We studied the membrane distribution of nicotinic acetylcholine receptors and α2 isoform of Na,K-ATPase in motor endplates of m. soleus in dysferlin-deficient Bla/J mice (a dysferlinopathy model). Endplates of Bla/J mice were characterized by increased area (without changes in fragmentation degree) and reduced density of the membrane distribution of nicotinic acetylcholine receptors in comparison with the corresponding parameters in control С57Bl/6 mice. The density of the membrane distribution of α2 isoform of Na,K-ATPase was also reduced, but the level of the corresponding mRNA remained unchanged. It can be hypothesized that abnormal membrane localization of α2 isoform of Na,K-ATPase results from adaptive skeletal muscle remodeling under conditions of chronic motor dysfunction.

Responses to noradrenaline of tail arteries in hypertensive, hypotensive and normotensive rats under different regimens of perfusion: role of the myogenic response.

The vasoconstrictor effects of noradrenaline were studied in spontaneously hypertensive rats (SHR) compared with Wistar Kyoto rats (WKY), and in Wistar rats with regional hypotension (WH) compared to control Wistar rats (WC). The abdominal aorta was ligated in WH distal to the renal arteries, lowering blood pressure in the hindquarters by 41% and tail artery wall cross-sectional area by 35% compared with WC. A cylindrical segment was dissected from the proximal part of the tail artery, cannulated at both ends and perfused with Krebs-Henseleit solution either at constant flow starting from a pressure of 120 mmHg or at a constant pressure of 120 mmHg. The cumulative dose-response relationships for noradrenaline were determined in control conditions and subsequently in the presence of gadolinium (100 microM), a non-specific blocker of mechanosensitive channels. Under constant-flow perfusion noradrenaline evoked a more prominent resistance increase in SHR compared with WKY and in WC compared with WH. Similar relations were seen in the presence of gadolinium, although responses were reduced. At constant pressure perfusion the vasoconstrictor response to noradrenaline was lower in SHR compared with WKY and in WC compared with WH. Application of gadolinium under constant-pressure perfusion reduced responses in WKY and WH, so that vasoconstriction in SHR became more pronounced than that in WKY and in WC than that in WH. It is suggested that the results can be explained by the difference in wall thickness causing different degrees of activation of the myogenic response to distension.

Effect of noradrenaline on tail arteries of SHR and WKY under perfusion at constant flow and constant pressure.

Vasoconstrictor effects of noradrenaline were compared in 6- to 7-month-old spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. A cylindrical segment was dissected from the proximal part of tail artery, cannulated at both ends and perfused alternately either at constant flow or constant pressure. Two series of experiments were performed. In the first series, vessels were perfused/superfused with Krebs-Henseleit solution. In the second one a modified salt solution was used, in which NaCl was totally replaced by an equimolar amount of KCI. Under constant flow conditions noradrenaline evoked a more prominent resistance increase in SHR compared with WKY independently of the composition of solution (normal or high-K+) used. At constant pressure perfusion with normal solution, the vasoconstrictor response to noradrenaline was more prominent in WKY. Under application of high-K+ solution, vasoconstriction at constant pressure in SHR became more pronounced than that in WKY. We suggest that there is greater wall thickness:lumen diameter ratio in SHR vessels and thus different contribution of distension-activated myogenic response is of primary importance for the data obtained.

[Attenuation of the efficacy of vasoconstrictive effects in rats after a 3-week suspension]. / Snizhenie éffektivnosti vazokonstriktornykh vliianii u krys posle 3-nedel'nogo vyveshivaniia.

Male Wistar rats were maintained suspended by the skin of posterior third of the back for three weeks. Constrictive reactions to norepinephrine and irritation of sympathetic nerves were studied with hindlimb vessels perfused with physiological solution at constant pressure. Perfusion pressure was stabilized at 40, 80, and 120 mmHg. During complete relaxation of the vascular smooth muscles the volumetric rate of perfusate flow in experimental animals was reduced comparing with their controls. This implies narrowing of the lumen in resistive vessels caused by suspension. Following suspension, reaction of rat's nerves to irritation was markedly lower than in the control at all levels of pressure. At 40 mmHg vessels of the suspended rats were more sensitive to norepinephrine; however, at 80 and 120 mmHg vascular sensitivity to the agent was reduced in the test group vs. the control. Suppression of the reactivity of hindlimb vessels to the constrictive agents may be one of the causes of failure of mechanisms of blood redistribution following prolonged gravitational deloading.