Search

The effects of short-term high-intensity exercise on single fiber contractile function in humans are unknown. Therefore, the purposes of this study were: (a) to access the acute effects of repeated high-intensity exercise on human single muscle fiber contractile function; and (b) to examine whether contractile function was affected by alterations in the redox balance. Eleven elite cross-country skiers performed four maximal bouts of 1300 m treadmill skiing with 45 min recovery. Contractile function of chemically skinned single fibers from triceps brachii was examined before the first and following the fourth sprint with respect to Ca(2+) sensitivity and maximal Ca(2+) -activated force. To investigate the oxidative effects of exercise on single fiber contractile function, a subset of fibers was incubated with dithiothreitol (DTT) before analysis. Ca(2+) sensitivity was enhanced by exercise in both MHC I (17%, P

Mutations in the gene for desmoplakin (DSP) may cause arrhythmogenic right ventricular cardiomyopathy (ARVC) and Carvajal syndrome (CS). Desmoplakin is part of all desmosomes, which are abundantly expressed in both myocardial and epidermal tissue and serve as intercellular mechanical junctions. This study aimed to investigate protein expression in myocardial and epidermal tissue of ARVC and CS patients carrying DSP mutations in order to elucidate potential molecular disease mechanisms. Genetic investigations identified three ARVC patients carrying different heterozygous DSP mutations in addition to a homozygous DSP mutation in a CS patient. The protein expression of DSP in mutation carriers was evaluated in biopsies from myocardial and epidermal tissue by immunohistochemistry. Keratinocyte cultures were established from skin biopsies of mutation carriers and characterized by reverse transcriptase polymerase chain reaction, western blotting, and protein mass spectrometry. The results showed that the mutation carriers had abnormal DSP expression in both myocardial and epidermal tissue. The investigations revealed that the disease mechanisms varied accordingly to the specific types of DSP mutation identified and included haploinsufficiency, dominant-negative effects, or a combination hereof. Furthermore, the results suggest that the keratinocytes cultured from patients are a valuable and easily accessible resource to elucidate the effects of desmosomal gene mutations in humans.

Whole body hematocrit/large vessel hematocrit (WBH/LVH ratio) has been examined in 21 normotensive and 35 hypertensive subjects and found to be the same, presumably as an expression of a uniform distribution of the blood volume in the two groups. Moderate renal impairment, the degree of the retinopathy, or the height of the diastolic blood pressure do not seem to influence the ratio figures. The WBH/LVH ratio was examined during treatment with various hypotensive drugs. A significant increase in the ratio was demonstrated during the influence of a single effective intravenous dose of pentolinium. Similar results were obtained during short-term treatment with guanethidine alone and during long-term treatment with guanethidine and hydrochlorothiazide. Treatment with hydrochlorothiazide alone caused an increase in ratio after one week and after three months, but these increases were not significant. The possible causes of these alterations in the WBH/LVH ratio are discussed. The advantage of employing a double isotope technique in preference to a quicker single isotope technique has been analyzed in relation to the determination of the total blood volume in patients during treatment with hypotensive drugs.

Short-term exercise produced a decrease in plasma volume and a rise in B.P. in normotensives and untreated hypertensive patients. The decrease in plasma volume is presumably due to an increased intra-capillary pressure in the contracting muscles. In guanethidine-treated patients there was no change in plasma volume during exercise, probably because of vasodilatation and decreased intra-capillary pressure in the contracting muscles. In several of the guanethidine-treated patients B.P. fell during and after exercise, in some cases so markedly that symptoms of cerebral ischemia developed.

Eleven patients with essential hypertension were treated with hydrochlorothiazide/KCl for three months. A significant fall in total blood volume, exchangeable sodium and blood pressure could be demonstrated both after one to two weeks and after three months of treatment, while a fall in serum sodium and body weight was only significant after one to two weeks of treatment. Thus, hypovolemia may, perhaps, be the explanation for the antipressor effect of thiazide even after three months of treatment.

1 Organ culture has been shown to upregulate both endothelin (ET) and 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptors in rat cerebral arteries. The purpose of the present study was to investigate the involvement of protein kinases, especially protein kinases C (PKC) and A (PKA) in this process. 2 The effect of inhibiting protein kinases during organ culture with staurosporine (unspecific protein kinase inhitor), RO 31-7549 (specific inhibitor of classical PKC's) and H 89 (specific inhibitor of PKA) was examined using in vitro pharmacological examination of cultured vessel segments with ET-1 (unspecific ET(A) and ET(B) agonist), S6c (specific ET(B) agonist) and 5-CT (5-HT(1) agonist). Levels of mRNA coding for the ET(A), ET(B), 5-HT(1B) and 5-HT(1D) receptors were analysed using real-time RT-PCR. 3 Classical PKC's are critically involved in the appearance of the ET(B) receptor; co-culture with RO 31-7549 abolished the contractile response (6.9+/-1.8%) and reduced the ET(B) receptor mRNA by 44+/-4% as compared to the cultured control. Correlation between decreased ET(B) receptor mRNA and abolished contractile function indicates upstream involvement of PKC. 4 Inhibition of PKA generally had an enhancing effect on the induced changes giving rise to a 7-25% increase in E(max) in response to ET-1, S6c and 5-CT as compared to the cultured control. 5 Staurosporine inhibited the culture induced upregulation of the response of both the ET(A) and the 5-HT(1B/1D) receptors, but had no significant effect on the mRNA levels of these receptors. This lack of correlation indicates an additional downstream involvement of protein kinases. British Journal of Pharmacology (2002) 137, 118-126. doi:10.1038/sj.bjp.0704838 (Less)