Acta physiologica Scandinavica最新文献

Force production of cardiac muscle is highly dependent on the interval between the excitations. The aim was to investigate relations between intracellular calcium ([Ca2+]i) and force when a stimulus protocol, with three extrasystoles (ESs) at various intervals, was used. The relation between [Ca2+]i and force was compared with that in frog skeletal muscle fibre. Fluo-3 was microinjected into thin cardiac trabeculae to monitor [Ca2+]i. During steady-state [Ca2+]i consisted of a rapid rise (phase 1) that lasted until peak dF/dt (rate of force development) and was followed by a slower rise (phase 2) that coincided with the action potential and had a peak after peak force. The decline in [Ca2+]i outlasted the duration of the contraction. As the ES intervals were prolonged, there was a gradual restitution of force and of the amplitude and rate of rise of phase 1 [Ca2+]i. Peak dF/dt was linearly related to the amplitude of phase 1 [Ca2+]i during restitution and potentiation of force. Skeletal muscle fibres were loaded with fluo-3-AM. From [Ca2+]i the amount of calcium bound to troponin ([Ca-T]) as a function of time was estimated. Force production of the skeletal muscle fibre could be predicted from [Ca-T] when the signal was delayed (time constant 36 ms). This finding indicates that the recorded [Ca2+]i in skeletal muscle represents activator calcium. In cardiac muscle probably only phase 1 [Ca2+]i represents activator calcium. Phase 2 [Ca2+]i probably represents calcium entry during the action potential and does not activate the contractile system to any significant extent.

The effect of AVP-V2 receptor agonist desmopressin, dDAVP, its non-peptide antagonist OPC-31260 and vehicle infusion on glomerular filtration rate (GFR) in the outer, middle and inner cortex was studied in both hydropenic and water diuretic Inactin anaesthetized female Sprague-Dawley rats using the aprotinin method. Two subsequent GFR measurements were carried out in the same kidney by injection of 125I- and 131I-labelled aprotinin before and after i.v. infusion of dDAVP, OPC-31260 or the vehicle. Acute infusion of dDAVP in hydropenic rats increased total GFR by 14% relative to vehicle infusion, whereas in water diuretic rats it had no effect relative to vehicle. No significant changes in arterial pressure (Pa) or renal blood flow (RBF) were recorded. Infusion of OPC-31260 reduced total GFR by 11% compared with vehicle. These results are consistent with the findings that a presensitization of the vasculature by high plasma levels of AVP is necessary for the renal vascular effects mediated by the V2 or V2-like receptors to occur. The ratio between inner and outer cortex GFR remained unchanged from control to experimental condition as follows: dDAVP infusion in hydropenic rats, 0.504 vs. 0.494 in control; vehicle infusion in hydropenic rats, 0. 393 vs. 0.392; OPC-31260 infusion in hydropenic rats, 0.517 vs. 0. 523; dDAVP in water diuretic rats, 0.547 vs. 0.543; vehicle in water diuretic rats, 0.413 vs. 0.417. Thus no significant difference in the GFR response was observed between superficial and deep cortical layers of the rat kidney.

We examined the effects of undernutrition on lipid metabolism in reindeer (<1 year) during mid-winter and spring, with particular focus on the proportions of polyunsaturated fatty acids (PUFAs) in major serum lipids. The reindeer (n=8) were fed their winter feed, lichen, ad libitum for 5 weeks, followed by 40% restriction of energy for 8 weeks and refeeding to normal for 6 weeks. The concentrations of major serum lipids, cholesterol and phospholipids decreased significantly during the ad libitum period (by 50 and 44%, respectively). The proportion of major PUFA, linoleic acid in serum cholesteryl esters, decreased from 48.2 to 38.4% during the ad libitum period (P < 0.01), and to 29.2% during the restriction period (P < 0.001). The proportion of linoleic acid in phospholipids decreased from 27.9 to 15.6% during the ad libitum period (P < 0. 001), and to 13.0% during the restriction (P < 0.01). Also alpha-linolenic acid in the major lipids decreased significantly during the ad libitum and restriction periods. The decreases in the major lipids and linoleic acid were reversed during the refeeding. The control group (n=8) which was fed high-quality concentrates ad libitum gained weight most of the spring but showed similar although slower decreases in the major serum lipids and PUFAs than the lichen group. Our results indicate that feeding reindeer on lichen during winter leads to the retardation of growth and reductions in major serum lipids and their principal C18-PUFA proportions. The decreased proportions of the principal PUFAs most probably reflect their low dietary intake but may have been modified also by seasonal factors.

Nitric oxide (NO) and epoxyeicosatrienoic acids (EETs), cytochrome P450 epoxygenase metabolites of arachidonic acid, are released by the vascular endothelium and play important roles in the control of glomerular haemodynamics. We examined whether endogenous NO or EETs modulate angiotensin II- (AngII) induced constriction in isolated microperfused afferent arteriole (Af-Art) of the rabbit kidney. When Af-Arts were treated with NG-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthese; 10-4 mol L-1) or miconazole (an inhibitor of P450 epoxygenase; 10-6 mol L-1), basal diameter was decreased by 34.5 +/- 2.2 and 13.9 +/- 3.2%, respectively. AngII added to both the bath and lumen decreased the diameter of Af-Arts in a dose-dependent manner. Pretreatment with either L-NAME or miconazole also augmented the constrictor response to AngII. AngII at 10-8 mol L-1 decreased the diameter to 39.2 +/- 1.4, 32.9 +/- 3.6, and 12.7 +/- 4.6%, in control, L-NAME-, and miconazole-treated group, respectively. In order to study whether the AngII type2 (AT2) receptor modulates AngII action via NO or EETs, we repeated the experiments in the presence of PD123319 (an AT2 receptor antagonist; 10-7 mol L-1). In the presence of PD123319, L-NAME still augmented the constrictor response to AngII, however, miconazole had no effect. In the presence of PD123319, AngII at 10-8 mol L-1 decreased the diameter to 25.0 +/- 4.6, 9.4 +/- 4.0, and 26.0 +/- 3.3%, in control, L-NAME-, and miconazole-treated group, respectively. These results suggest that (1) tonic release of NO and EETs attenuates the vasoconstrictor response to AngII in Af-Arts and (2) AT2 receptor seems to be coupled to EETs rather than the NO pathway.

Acute unilateral renal denervation (aDNX) is associated with reduced tubuloglomerular feedback (TGF) sensitivity. Six days after denervation (cDNX) TGF sensitivity is somewhat restored, but TGF reactivity increased. This study aimed to investigate if the increased TGF reactivity that was seen in cDNX kidneys was owing to reduced production of nitric oxide (NO). TGF characteristics were determined with micropuncture experiments in anaesthetized rats, using the stop-flow pressure (PSF) technique. Maximal drop in PSF (DeltaPSF) was used as an index of TGF reactivity and the loop of Henle perfusion rate that elicited half-maximal DeltaPSF, the turning point (TP) was used as a measure of TGF sensitivity. In cDNX kidneys, TP was higher than in control rats (25.4 +/- 1.5 nL min-1 vs. 19.1 +/- 1.1 nL min-1), but clearly lower than in aDNX rats (37. 3 +/- 3.1 nL min-1). TGF was more reactive in cDNX rats (DeltaPSF=14. 7 +/- 1.1 mmHg) than in aDNX (7.9 +/- 1.1 mmHg) and control rats (9. 6 +/- 0.9 mmHg). Intratubular inhibition of NO synthase N omega-nitro-L-arginine (L-NA) in sham-DNX animals, decreased TP to 13.9 +/- 2.2 nL min-1 and DeltaPSF was increased with 92%. In cDNX kidneys TP was not significantly reduced by L-NA, and TGF reactivity was only moderately increased by 31%. Intratubular infusion of L-arginine (L-Arg) reduced DeltaPSF from 10.2 +/- 0.7 to 6.5 +/- 0.6 mmHg in sham-DNX kidneys, but TP was unaffected. In cDNX kidneys, there was no effect on either DeltaPSF or TP by the addition of L-Arg. However, when NO was delivered via sodium nitroprusside in the tubular perfusate, a clear reduction of DeltaPSF was seen in both sham-DNX and cDNX kidneys (from 9.9 +/- 0.5 to 4.4 +/- 1.0 and from14.9 +/- 1.3 to 8.1 +/- 1.5 mmHg, respectively). This indicates that cDNX is a state of low renal NO production and that this low level of NO resets TGF to a higher sensitivity and more pronounced reactivity.

Force and speed parameters were obtained from isometric contractions at different stimulation frequencies of creatine kinase-deficient and wildtype in situ mouse medial gastrocnemius muscles. The absence of creatine kinase did not affect force production at higher stimulation frequencies. However, at frequencies below 140 Hz, forces were lower than the controls (P < 0.05); at the lowest frequency applied (80 Hz) the force was reduced to approximately 60% compared with the wildtype muscles. In contrast, twitch force was not affected. When the contractions were preceded by a brief tetanus (50 ms), the effects of lacking creatine kinase on force production were more pronounced; at 80 Hz stimulation isometric force was further reduced to 66.5 +/- 6.2% (mean +/- SD; n=5) of the single contractions of the deficient muscles and to approximately 42% of the wildtype muscles. Twitch force was now also reduced (by approximately 50%) after the tetanus. The speed of the muscles was not affected in the single contractions. However, after a preceding tetanus, the rate of force rise was reduced by approximately 14% at high frequencies of stimulation. With decreasing frequencies (below 250 Hz), the reduction in speed became more pronounced; at 80 Hz the rate in the creatine kinase-deficient muscles was only 55.2 +/- 3.9% (mean +/- SD; n=5) of the wildtype muscles. No effects of the deficiency were found for the half relaxation times. The data suggest that an impaired creatine kinase system leads to lower activation levels at submaximal stimulation frequencies, possibly by a reduction in Ca2+-release during repetitive stimulation. Similar effects may be expected in normal fatigued muscle when phosphocreatine is depleted.

The effect of the local anaesthetics lidocaine, its meta-isomer, LL33, bupivacaine, tetracaine and procaine on the transducer properties of the stretch receptor neurone of the crayfish Pacifastacus leniusculus was investigated using a two microelectrode voltage clamp. Lidocaine increased the receptor current whereas LL33, bupivacaine and tetracaine reduced the receptor current in a reversible dose-dependent way. Procaine did not affect the receptor responses. The onset of the effect was generally slow in the order of minutes. Lidocaine increased the conductance of the mechanotransducer 50 +/- 7% (mean +/- SD, n = 4) and changed the reversal potential -8 +/- 1 mV (mean +/- SEM, n = 8), which indicates a major K+ conductance increase through the mechanosensitive channels. The other local anaesthetics increase the K+ conductance of the mechanotransducer without increasing the total conductance, which suggests that only P(Na)/P(K) is changed. These substances seem to have a Ca2+ dependent effect on the gating properties of the mechanosensitive channels in addition to their effect on the permeability through the channels as compared with lidocaine. All local anaesthetics investigated decreased the leak conductance of the receptor neurone. The effects of local anaesthetics on the mechanosensitive channels whether activating or blocking is correlated to the oil:water distribution coefficients and their relative hydrophobicity/hydrophilicity ratio. The results are consistent with the hypothesis that the local anaesthetic effect is mediated by changes in the lipid phase of the membrane.