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mmol/L KCl (l + kcl)
Selected AbstractsMechanisms of glutamate release elicited in rat cerebrocortical nerve endings by ,pathologically' elevated extraterminal K+ concentrationsJOURNAL OF NEUROCHEMISTRY, Issue 3 2007Luca Raiteri Abstract Extracellular [K+] can increase during some pathological conditions, resulting into excessive glutamate release through multiple mechanisms. We here investigate the overflow of [3H]d -aspartate ([3H] d -ASP) and of endogenous glutamate elicited by increasing [K+] from purified rat cerebrocortical synaptosomes. Depolarization with [K+] , 15 mmol/L provoked [3H] d -ASP and glutamate overflows almost totally dependent on external Ca2+. Consistent with release by exocytosis, the overflow of [3H] d -ASP evoked by 12 mmol/L K+ was sensitive to clostridial toxins. The overflows evoked by 35/50 mmol/L K+ remained external Ca2+ -dependent by more than 50%. The Ca2+ -independent components of the [3H] d -ASP overflows evoked by [K+] > 15 mmol/L were prevented by the glutamate transporter inhibitors dl - threo -beta-benzyloxyaspartate (dl -TBOA) and dihydrokainate. Differently, the overflows of endogenous glutamate provoked by [K+] > 15 mmol/L were insensitive to both inhibitors; the external Ca2+ -independent glutamate overflow caused by 50 mmol/L KCl was prevented by bafilomycin, by chelating intraterminal Ca2+, by blocking the mitochondrial Na+/Ca2+ exchanger and, for a small portion, by blocking anion channels. In contrast to purified synaptosomes, the 50 mmol/L K+ -evoked release of endogenous glutamate or [3H]D-ASP was inhibited by dl -TBOA in crude synaptosomes; moreover, it was external Ca2+ -insensitive and blocked by dl -TBOA in purified gliosomes, suggesting that carrier-mediated release of endogenous glutamate provoked by excessive [K+] in CNS tissues largely originates from glia. [source] COMPARATIVE EFFECTS OF TRAMADOL ON VASCULAR REACTIVITY IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2008Juliana M Raimundo SUMMARY 1The aim of the present study was to determine the effects of tramadol on vascular reactivity in aortic rings from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2Aortic rings, with or without endothelium, were obtained from male WKY rats and SHR (15,20 weeks old) and prepared for isometric tension recording. Aortic rings were precontracted with phenylephrine (10 µmol/L) or 40 mmol/L KCl and then exposed to cumulative concentrations of tramadol (0.1,1 mmol/L). 3Tramadol produced a concentration-dependent relaxation of precontracted aortic rings from WKY rats and SHR, which was not dependent on functional endothelium. Vascular relaxation was significantly greater in rings from SHR than WKY rats. 4The concentration of tramadol necessary to produce a 50% reduction of the maximal contraction to phenylephrine (IC50) in rings with and without endothelium from SHR was 0.47 ± 0.08 and 0.44 ± 0.03 mmol/L, respectively (P = 0.76). 5Tramadol attenuated the contracture elicited by Ca2+ in depolarized tissue, suggesting that it may inhibit L-type Ca2+ channels. However, pretreatment with nicardipine (1 µmol/L) prevented the relaxation induced by tramadol in aortic rings from WKY rats and partially reduced its inhibitory effect in aortic rings from SHR. 6Pretreatment of endothelium-denuded aorta with glybenclamide (3 µmol/L), 4-aminopyridine (3 mmol/L), tetraethylammonium (3 mmol/L) and naloxone (100 µmol/L) did not affect tramadol-induced vasodilation of aortic rings from either WKY rats or SHR. 7Intravenous administration of tramadol (10 mg/kg) to conscious SHR significantly reduced both systolic and diastolic blood pressure from 171.4 ± 5.3 to 129.3 ± 5.3 (P = 0.002) and from 125.0 ± 6.5 to 57.8 ± 8.9 mmHg (P = 0.003), respectively. [source] Cysteinyl leukotrienes and leukotriene B4 mediate vasoconstriction to arginine vasopressin in rat basilar arteryCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2005Cristina C Trandafir Summary 1.,Arginine vasopressin (AVP) has been reported to be involved in the development of cerebral vasospasm after haemorrhage and cerebral oedema following ischaemia. Endogenously produced 5-lipoxygenase metabolites are able to contract isolated endothelium-preserved arterial strips and modulate vascular permeability. The present study addresses the role of 5-lipoxygenase and its products, namely cysteinyl leukotrienes (CysLTs) and leukotriene (LT) B4, in the contraction induced by AVP in rat basilar artery. 2.,Contractile responses to LTD4, LTC4, LTB4 or AVP were assessed in spiral preparations of rat endothelium-intact basilar artery. Contractions to AVP were determined in the absence or presence of 5-lipoxygenase inhibitors or CysLT1 or BLT receptor antagonists. Contractile responses to leukotrienes and AVP are expressed as a percentage of the contraction induced by 80 mmol/L KCl. 3.,Leukotriene D4, LTC4 and LTB4 acted as vasoconstrictor agents in rat basilar artery, causing contractions (all at concentrations of 1 µmol/L) of 42 ± 13, 54 ± 15 and 25 ± 6% of the response to 80 mmol/L KCl, respectively. A concentration,response curve was constructed for AVP over the range 1 pmol/L to 10 nmol/L and an EC50 value of 0.19 ± 0.02 nmol/L (n = 30) was determinted. The presence of the 5-lipoxygenase inhibitors ZM 230487 (10 nmol/L and 0.1 and 1 µmol/L) and AA 861 (1, 3, 10, and 30 µmol/L), the CysLT1 receptor antagonist MK 571 (3, 10 and 30 µmol/L) or the BLT receptor antagonists CP 105696 and LY 255283 (3, 10 and 30 µmol/L for both) in the organ bath significantly attenuated the contractions induced by AVP in rat basilar artery (P < 0.05). 4.,The experimental results of the present study provide the first evidence for the involvement of CysLTs and LTB4 in the in vitro constriction induced by AVP in rat basilar artery. In the context of previously reported involvement of AVP in the development of cerebral vasospasm and oedema, the present study draws attention to the potential role played by the 5-lipoxygenase pathway in these pathological processes. [source] Spasmogenic action of endothelin-1 on isolated equine pulmonary artery and bronchusEQUINE VETERINARY JOURNAL, Issue 2 2003A. E. M. BENAMOU Summary Reasons for performing study: There is currently little published information about the effects of endothelin-1 (ET-1), a potent endogenous spasmogen of vascular and airway smooth muscle, on pulmonary vasculature and airways or which ET receptor subtypes mediate ET-1-induced vasoconstrictive and bronchoconstrictive action in the horse. Objectives: To investigate the effect of endothelin-1 (ET-1) on smooth muscle from isolated equine pulmonary artery and bronchus. In addition, the roles of ETA and ETB receptors in ET-1 mediated contraction in these tissues were assessed. Methods: The force generation of ring segments from pulmonary arteries or third-generation airways (obtained from horses subjected to euthanasia fororthopaedic reasons) were studied in an organ bath at 37°C in response to exogenous endothelin and selective endothelin A (BQ123) or B receptor (BQ788) antagonists. Results: ET-1 produced concentration-dependent contractions of the equine pulmonary artery and bronchus. The threshold for contraction was 10,10 and 10,9 mol/l ET-1 for pulmonary artery and bronchus, respectively. The maximal contraction induced by the highest ET-1 concentration (10,7 mol/l) was 173 and 194% of the contraction obtained with 100 mmol/l KCl in pulmonary artery and bronchus, respectively. ET-1 potency was 25 times greater in equine pulmonary artery than in equine bronchus (concentration of ET-1 producing 50% of maximal contraction [EC50] = 5.6 10,9 mol/l and 2.2 10,8 mol/l, respectively). In pulmonary artery, ET-1 induced contractions were significantly inhibited by the ETA receptor antagonist BQ123 (1 ,mol/l; dose-response curve to ET-1 was shifted to the right by 5.4-fold), but not by the ETB antagonist BQ788. In bronchus, dose-responses curves to ET-1 were shifted to the right by BQ123 (1 ,mol/l; 2.5-fold), but not by BQ788 (1 ,mol/l). In the presence of both antagonists, the dose-response curve to ET-1 was shifted to the right by 4.5-fold. Conclusions: These functional studies demonstrate that ET-1 is a potent spasmogen of equine third generation pulmonary artery and bronchus, and that contractions are mediated via ETA receptors in the former and both ETA and ETB receptors in the latter. Potential clinical relevance: Endothelin receptor antagonists may have potential for treating equine pulmonary hypertension or bronchoconstriction. [source] | ||||||||||