The effect of long-term inhibition of nitric oxide synthase on the relaxation and contraction ability of the thoracic aorta, carotid and pulmonary arteries was studied in the early postnatal period. Starting from the fifth day after birth, puppies were administered NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day subcutaneously) for 6 weeks. After this period, mean blood pressure increased from the control value of 94±14 mm Hg to 168±5 mm Hg (P<0.01) and the heart/body weight ratio from 6.22±0.25 to 8.23±0.45 (PcO.Ol). In control arterial rings precontracted by phenylephrine (10“5 mol/1), acetylcholine caused dose-dependent relaxations; the maximal values were reached in the range of 10 "8 to 10"* mol/1. In arteries from L-NAME treated puppies, acetylcholine also induced dose-dependent relaxations, the maximum values in the thoracic aorta (81.0±2.9 %) and carotid artery (87.2±6.9 %) were significantly reduced, not, however, in the pulmonary artery (76.4±7.8 %). Dose-response curves to acetylcholine in all the examined arteries from L-NAME-treated animals were shifted to the right indicating a decrease in sensitivity to acetylcholine. Neurogenic contractions, induced by electrical stimulation of adrenergic nerves, were not significantly altered in the thoracic aorta and carotid artery. However, in the pulmonary artery the contractions were greater at high frequency of stimulation. The findings that (i) submaximal doses of L-NAME attenuate acetylcholine-induced relaxation only slightly, and (ii) that it does not appreciably influence adrenergic contractions justify the hypothesis that the endothelium of vessels in newborn dogs is very probably endowed with a high content of nitric oxide synthase.
Vascular stenosis is often described only by its percentage in both clinical and scientific praxis. Previous studies gave inconclusive results regarding the effect of stenosis eccentricity on its hemodynamic effect. The aim of this experimental study was to investigate and quantify the effect of stenosis severity and eccentricity on the pressure drop. A combination of pressure and flow measurements by Par ticle Imaging Velocimetry (PIV) method was used. Models of the same stenosis significance but with different levels of eccentricity were studied in vitro by PIV. This study has shown that stenosis asymmetry is associated with more profound pressure drop an d flow volume decrease. On the contrary, pressure drop and flow volume decrease were not further significantly influenced by the level of asymmetry. Hemodynamic changes associated with stenosis eccentricity must be taken into account in both clinical and s cientific studies., L. Novakova, J. Kolinsky, J. Adamec, J. Kudlicka, J. Malik., and Obsahuje bibliografii
The effects of transient and sustained hyperthyroidism on vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) levels were studied in the heart atria of developing and adult rats. Newborn rats were divided into 5 groups. Neo-T animals were treated with thyroxine (T4) during postnatal days 1-8 and sacrificed at the age of 60 days. Neo-S rats were treated with T4 during postnatal days 1-60 and sacrificed one day later. Adult-1 and Adult-2 animals received T4 during days 52-60 and were sacrificed 5-6 days and 1 day later, respectively. Control animals were injected with saline. VIP-LI concentrations were determined in extracts from the left and right atria separately. In Neo-S and Adult-2 rats, spontaneous heart rate, the weight of both atria and total T4 serum levels were significantly enhanced, while their body weight was decreased. The ratio atria weight to body weight was significantly increased in all groups except for Adult-1 animals. Hyperthyroidism led to a significant decrease in VIP-LI levels in both atria of Neo-S and Neo-T rats. Hyperthyroidism induced in adult rats also decreased VIP-LI levels in both atria. However, this change was only transient. In conclusion, our data have provided new evidence that hyperthyroidism induced during the early neonatal period interferes with the development of VIP-ergic innervation in rat atria. The period of the first few postnatal days seems to be essential for this effect, since VIP-LI concentrations in 60-day-old animals did not significantly differ between Neo-S and Neo-T atria., J. Kuncová, J. Slavíková., and Obsahuje bibliografii
The pulmonary vasodilator action of an S-nitrosothiol, S-nitroso acetylpenicillamine (SNAP), was investigated in the rat pulmonary vasculature. The influence of its nitric oxide donator property was studied by comparison with the effect of acetylpenicillamine (AP), SNAP minus the nitroso group, and the blockade of nitric oxide release by the L-arginine analogue, L-NAME. In the isolated rat lung perfused with autologous blood at a constant flow rate (1PL), changes in pulmonary artery pressure (Ppa) reflect changes in pulmonary vascular resistance. Dose-response relationships to both SNAP and AP (0.1, 1, 10 and 100 /ug) were established both during normoxic ventilation (air + 5 % CO2; low Ppa) and when Ppa was raised by alveolar hypoxic vasoconstriction (2 % O2 + 5 % CO2). SNAP caused small dose-dependent fall in normoxic Ppa (mean±S.D. 17.4±3.0 mm Hg). in 11 rat IPL % fall of Ppa was 1, 3 and 4 % for 1, 10 and 100 ¡ug, respectively (p<0.01). This fall was more obvious when Ppa was raised by hypoxia (mean Ppa rise (HPV) 11.5±3.8 mm Hg); there was a 22, 55 and 79 % fall in HPV for 1,10 and 100 /ug in 11 rat IPL. The dilatation after 10 /ig SNAP was not consistently affected by 100/rg L-NAME (% fall in HPV pre L-NAME 45±22 % vs 42±23 % post L-NAME). AP had no significant effect on Ppa, causing only small falls in Ppa, equivalent to solvent (saline). There was occasionally a small rise in Ppa with 10 and 100 /tg AP. Thus, the dilator action of SNAP is most likely due to its NO donator property, and is not consistently affected by blockade of endogenous NO release.
Pathophysiological mechanisms underlying the development of renal dysfunction and progression of congestive heart failure (CHF) remain poorly understood. Recent studies have revealed striking differences in the rol e of epoxyeicosatrienoic acids (EETs), active products of cytochrome P-450-dependent epoxygenase pathway of arachidonic acid, in the progression of aorto-caval fistula (ACF)-induced CHF between hypertensive Ren-2 renin transgenic rats (TGR) and transgene-negative normotensive Hannover Sprague-Dawley (HanSD) controls. Both ACF TGR and ACF HanSD strains exhibited marked intrarenal EETs deficiency and impairment of renal function, and in both strains chronic pharmacologic inhibition of s oluble epoxide hydrola se (sEH) (which normally degrades EETs) normalized EETs levels. However, the treatment improved the survival rate and attenuated renal function impairment in ACF TGR only. Here we aimed to establish if the reported improved renal function and attenuation o f progression of CHF in ACF TGR observed after sEH blockade depends on increased vasodilatory responsiveness of renal resistance arteries to EETs. Therefore, we examined the responses of interlobar arteries from kidneys of ACF TGR and ACF HanSD rats to EET-A, a new stable 14,15-EET analog. We found that the arteries from ACF HanSD kidneys rats exhibited greater vasodilator responses when compared to the ACF TGR arteries. Hence, reduced renal vasodilatory responsiveness cannot be responsible for the lack of beneficial effects of chronic sEH inhibition on the development of renal dysfunction and progression of CHF in ACF HanSD rats., A. Sporková, Z. Husková, P. Škaroupková, N. Rami Reddy, J. R. Falck, J. Sadowski, L. Červenka., and Obsahuje bibliografii
Previous studies have substantiated the antipyretic role played by extrahypothalamic limbic system (EXHY-LS) AVP during fever. Repeated attempts to elucidate other thermoregulatory functions of this hormone have failed. Circumstantial evidence, however, suggest central role for this hormone in thermoregulation under hypohydration. Hypohydration, hyperosmolarity and hypovolaemia induce upward shifts in temperature thresholds for activation of heat dissipating mechanisms. When hypovolaemia is superimposed on hyperosmolarity these shifts are additive. Analogously, these two stressors when combined, decrease the osmotic threshold for AVP release. In rats, the elevated temperature thresholds for evaporative cooling and peripheral vasodilation occurring with hypohydration are positively correlated with lower Hypothalamic/EXHY-LS AVP ratio. Reciprocal relations between limbic system and blood AVP contents suggest competitive interaction between central and peripheral demands. Hypothesis for the possible mode of action of central AVP in thermoregulation under hypohydration is discussed.
The potassium channel opening drug, pinacidil, has been examined in isolated perfused lungs taken from rats with hypoxic pulmonary hypertension (housed in 10 % oxygen for 7 days) and control rats. Inhibition by pinacidil (1 to 30 //M) of noradrenaline (NA)-induced vasoconstriction (NA infusions; /^-adrenoceptors blocked) and of hypoxic pulmonary vasoconstriction (HPV; ventilation for 3.5 -4.5 min with 0-1 % oxygen) were compared. The vasoconstrictor responses in preparations from control and hypoxic rats, respectively, were (mm Hg) NA 6.6±0.68 (6); 8.2±1.45 (9); HPV 7.8±1.03 (12); 8.8±0.93 (13). These responses were reversibly inhibited by pinacidil. In lungs from control rats pinacidil was 10-fold less potent against NA than against HPV, but in lungs from hypoxic rats it was equipotent against NA and HPV. When tested against NA, but not HPV, pinacidil was significantly more potent in lungs from hypoxic rats than control rats. It is postulated that NA-induced vasoconstriction in lungs from hypoxic rats, and HPV in both groups of rats, involve calcium influx through voltage-operated calcium channels. Consequently, these responses are readily inhibited by drugs such as pinacidil which open potassium channels and hyperpolarise the cell membrane. In contrast in lungs from control rats, NA-induced constriction may involve mainly intracellular calcium release and thus be less readily inhibited by the hyperpolarising effect of pinacidil.
The aim of this study was to test the hypothesis that vasorelaxing action of vasonatrin peptide (VNP) is due to activation of the large-conductance Ca2+-activated potassium channel (BKCa) via guanylyl cyclase (GC)-coupled natriuretic peptide receptors (NPRs) in vascular smooth muscle cells (VSMCs). Contraction experiments were performed using human radial artery, whereas BKCa current by patch clamp was recorded in cells from rat mesenteric artery. Contractility of rings cut from human radial artery was detected in vitro. As a result, VNP induced a dose-dependent vasorelaxation of human radial artery, which could be mimicked by 8-Br-cGMP, and suppressed by TEA, a blocker of BKCa, HS-142-1, a blocker of GC-coupled NPRs, or methylene blue (MB), a selective inhibitor of guanylyl cyclase. Sequentially, whole-cell K+ currents were recorded using patch clamp techniques. BKCa current of VSMCs isolated from rat mesentery artery was obtained by subtracting the whole cell currents after applications of 10-7 mol/l iberiotoxin (IBX) from before its applications. In accordance with the results of arterial tension detection, BKCa current was significantly magnified by VNP, which could also be mimicked by 8-Br-cGMP, whereas suppressed by HS-142-1, or MB. Taken together, VNP acts as a potent vasodilator, and NPRA/B-cGMP-BKCa is one possible signaling system involved in VNP induced relaxation., J. Yu ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
A brief nomenclatural history of Vavraia culicis (Weiser, 1947), the type species for the genus Vavraia Weiser, 1977, is presented together with a detailed description of the cytological and ultrastructural characteristics of a Vavraia culicis-like microsporidian species isolated from Aedes albopictus (Scuse) in Florida. This ''Florida isolate'', is the only known isolate of a species of the genus Vavraia from mosquitoes propagated in laboratory culture. Although the Florida isolate has been used under the name Vavraia culicis in several molecular phylogeny and host-parasite studies, it has not been structurally characterized and its relationship to the type species Vavraia culicis has never been examined. Structural data strongly support placement of the Florida isolate within the genus Vavraia and indicate its close relationship to both the type species of the genus and to other Vavraia-like mosquito microsporidia to which the name V. culicis has been applied. However, the identity of the Florida isolate with V. culicis (Weiser, 1947) Weiser, 1977 cannot be presently confirmed. Morphometric examination of spores of several Vavraia-like microsporidia isolates from mosquitoes, including the type material of Vavraia culicis, indicates that Vavraia culicis-like microsporidia probably represent not a single species, but a group of closely related organisms. Subspecies status is proposed for the Florida isolate.
Ernst Mach was already an internationally recognised experimental physicist, when he, after professorships for Mathematics and Physics in Graz and Experimental Physics in Prague, took over the chair for "Philosophy, particularly for the History and Theory of the Inductive Sciences", at the University of Vienna in 1895. This turn from natural sciences to philosophy was really an exception in the academic field. Although he was not a specialist in philosophy his ideas exhibited a remarkable influence. Here is the first part of the author's text, the second, closing part (Mach and Philosophy) will be published in the next issue of this Journal., Friedrich Stadler ; z angličtiny a němčiny přeložil M. Černohorský., and Obsahuje bibliografii