1 Vascular contractions induced by K+-free solution and relaxation responses following the return of K+ to the organ bath were studied in mesenteric arterial rings from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with particular focus on the role of vascular adrenergic nerve-endings and endothelium. 2 In endothelium-denuded rings the omission of K+ from the incubation medium resulted in gradual contractions, the rate of which was slower in SHR than WKY. Nifedipine (1 ALM) inhibited the contractions more effectively in SHR than WKY. 3 Adrenergic denervation in vitro with 6-hydroxydopamine reduced the contractions induced by the K+-free medium in endothelium-denuded rings. The remaining contractions after denervation were markedly greater in SHR than WKY. 4 The presence of intact vascular endothelium attenuated the K+-free contractions in both strains, the attenuation being smaller in SHR than WKY. N0-nitro-L-arginine methyl ester (L-NAME, 0.1 mM) and methylene blue (10 fiM), but not indomethacin (10 JM), abolished the attenuating effect of endothelium on the K+-free contractions. L-Arginine (1 mM) reversed the effect of L-NAME in WKY but not in SHR. 5 The re-addition of K+ after full K+-free contractions dose-dependently relaxed the rings. The rate of this K+-induced relaxation was significantly slower in SHR than WKY at all K+ concentrations (0.1-5.9 mM) studied, whether the endothelium or functioning adrenergic nerve-endings were present or not. Ouabain (1 mM) totally inhibited the K+ relaxation in SHR but only partially in WKY. 6 Vascular smooth muscle contractions induced by high concentrations of potassium were comparable between the strains. The EC50 for noradrenaline-induced contractions was lower in SHR than WKY, but the maximal forces did not differ significantly. 7 In conclusion, the contractile response in K+-free solution more clearly differentiates vascular rings from SHR and WKY than the responses induced by the classical contractile agents noradrenaline and high concentrations of potassium. The depressant effect of the presence of intact endothelium on the K+-free contractions, which was smaller in SHR than WKY, is mediated via the endothelium-derived relaxing factor. Neurotransmitter release from vascular adrenergic nerve-endings participates less in the K+-free contractile response in SHR than WKY. Moreover, the contractile response is more dependent on calcium entry through nifedipine-sensitive calcium channels in SHR than WKY. The greater K+-free contractions of denervated endothelium-denuded rings and the reduced K+ relaxation rate in SHR when compared to WKY suggest increased cell membrane permeability and decreased activity of vascular Na+, K+-ATPase, respectively, in this type of genetic hypertension.

1 The effects of long-term angiotensin-converting enzyme inhibition with quinapril on arterial function were studied in spontaneously hypertensive rats, Wistar-Kyoto rats serving as normotensive controls. 2 Adult hypertensive animals were treated with quinapril (10 mg kg-' day-') for 15 weeks, which reduced their blood pressure and the concentrations of atrial natriuretic peptide in plasma and ventricular tissue to a level comparable with that in normotensive rats. 3 Responses of mesenteric arterial rings in vitro were examined at the end of the study. Compared with normotensive and untreated hypertensive rats, responses to noradrenaline were attenuated in hypertensive animals on quinapril, both force of contraction and sensitivity being reduced. Quinapril also attenuated maximal contractions but not sensitivity to potassium chloride. Nifedipine less effectively inhibited vascular contractions in normotensive and quinapril-treated than in untreated hypertensive rats. 4 Arterial relaxation responses by endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitrite, isoprenaline) mechanisms were similar in normotensive and quinapril-treated rats and more pronounced than in untreated hypertensive rats. 5Cell membrane permeability to ions was evaluated by means of potassium-free solution-induced contractions of endothelium-denuded denervated arterial rings. These responses were comparable in normotensive and quinapril-treated rats and less marked than in untreated hypertensive rats. 6 Intracellular free calcium concentrations in platelets and lymphocytes, measured by the fluorescent indicator quin-2, were similar in normotensive and quinapril-treated rats and lower than in untreated hypertensive rats. 7 In conclusion, quinapril treatment improved relaxation responses and attenuated contractions in arterial smooth muscle of hypertensive rats. These changes may be explained by diminished cytosolic free calcium concentration, reduced cell membrane permeability, and alterations in dihydropyridinesensitive calcium channels following long-term angiotensin-converting enzyme inhibition.

Heat shock protein 90 (hsp90) is associated with many steroid receptors in tissue homogenates. It is widely accepted that hsp90 regulates the binding of the receptor to the corresponding gene regulatory element. However there is no unequivocal evidence that steroid receptor-hsp90 complexes are present in the intact cells. We demonstrate here the absence of progesterone receptor (PR)-hsp90 complexes in intact target cell nuclei, using immunohistochemical and biochemical methods to determine the location and composition of the nonliganded (aporeceptor) and liganded (holoreceptor) PR complexes. In the chicken oviduct ceUls, both apo-and holoreceptors were nuclear, while hsp90 was exdusively cytoplasmic.

Almost 30 years have passed since the original demonstration that steroid receptors, comprising a subfamily of the nuclear receptor (NR) superfamily, exist as large (6-8S) non-DNA-binding complexes in hypotonic extracts (cytosol) of target cells; later such complexes were shown to correspond to a heterooligomer composed of receptor, heat shock (Hsp), and other proteins. Subsequently, an impressive number of studies have dealt with the composition of the "nonactive" complex, its dissociation and/or reassembly in vitro, possible functions of the non-receptor components, and their subcellular compartmentalization. While there is little dispute about the chaperoning role of some Hsps in such a complex, there is still no final proof of an association in vivo of NRs and Hsps in the nuclei of target cells, which is requisite for a direct regulatory involvement of Hsps in NR function. Here we critically review the various models that have been put forward to attribute a biological function to the NR-Hsp90 interaction, evaluate the corresponding experimental data, and integrate recent concepts originating from the structural and functional analyses of NRs.

Cold panniculitis in horse riders, also known as horse rider's pernio or equestrian panniculitis, is a rare phenomenon. Most published reports present only a few patients (1-5). Cold-induced pernio has also been reported in cyclists, motorists, milk-delivery men, golf-buggy drivers, and, in the context of other outdoor activities practised in wet and windy conditions (6), in both males and females (7). We describe here 3 patients, and an estimate of the prevalence of, and predisposing factors for, cold panniculitis among Finnish stable owners and their personnel based on a questionnaire study. CASE REPORT AND METhODSWe recently diagnosed cold panniculitis in three female horse riders (aged 18, 28 and 33 years), who had been riding for 10-20 years. They experienced skin symptoms during the cold winter months (from November to May) in particular (Fig. 1). The haematological and immunological parameters studied were normal (i.e. blood cell count, erythrocyte sedimentation rate, serum creatinine, creatine kinase, alanine amino-transferase, amylase, thyroid stimulating hormone, free thyroxin, rheumatoid factor, cold agglutinins, cryoglobulins, immunoglobulins (G, A, M), serum protein electrophoresis, components of complement (C3, C4), antinuclear antibodies, antibodies against extractable nuclear antigens and double-stranded DNA antigens, anticardiolipin antibodies, anti-β 2 -glycoprotein antibodies, and antineutrophil cytoplasmic antibodies). They did not experience any other disease in addition to the skin symptoms.To examine the prevalence of cold panniculitis among horse riders, we sent an e-mail questionnaire on skin symptoms to the members of the Equestrian Federation of Finland (n = 234). Two photographs of typical equestrian panniculitis, with ulcerating or oozing raised plaques, redness and hyperpigmentation on the lateral side of a thigh were included with the questionnaire in order to help the respondents recognize the symptoms.Statistical analyses of the results were performed using statistical package SSPS 15.0 software (SSPS Inc., Chicago, IL, USA), applying cross-tabulation, χ 2 test, Student's t-test, Mann-Whitney U test and logistic regression. RESULTSOf the 234 questionnaires sent, 110 (47%) were returned. Three answers were incomplete. Thus, 107 answers (46%) were included in the analyses. Twenty-five (25%) respondents reported panniculitis-like skin symptoms during the winter. One-third of the riders reported the symptoms starting in October, and being worst in January and February (the coldest months of the year in Finland). One-fifth still had symptoms in March. The riders with symptoms were significantly younger than those who were symptomless (p = 0.018).Those who smoked more than 10 cigarettes daily had symptoms significantly more often than non-smokers (p = 0.025). In addition, riders under 35 years of age and those who wore tight riding clothes for the whole working day (not only when riding) were at risk of skin symptoms (p = 0.018 and p = 0.005, respectively).