The Experts below are selected from a list of 249 Experts worldwide ranked by ideXlab platform

Jeanclaude Stoclet - One of the best experts on this subject based on the ideXlab platform.

G S Stokes - One of the best experts on this subject based on the ideXlab platform.

  • Interaction between Ca2+, verapamil, and ketanserin in rat Tail Artery and aorta.
    Journal of cardiovascular pharmacology, 1995
    Co-Authors: John F Marwood, G S Stokes
    Abstract:

    To elucidate the complex pharmacological actions of the 5-hydroxytryptaminezA (5-HT 2A )-receptor antagonist ketanserin, we investigated certain similarities between these properties and those of the Ca antagonist verapamil. We investigated the interactions of Ca 2+ , ketanserin, and verapamil on the contractile responses to 5-HT in rat isolated perfused Tail Artery and aortic strip preparations. In both tissues, variations in perfusate [Ca 2+ ] had similar effects: threshold contractile concentrations of 5-HT were unaffected, and the upper ends of the 5-HT dose-response curves were augmented or decreased by increased or decreased [Ca 2+ ], respectively. Ketanserin competitively antagonised contractile responses to 5-HT in both tissues, with mean pA 2 values of 9. 17 and 7.46 in Tail Artery and aorta, respectively. However, increase in [Ca 2+ ], with addition of ketanserin, caused a parallel leftward shift of the 5-HT dose-response curve in Tail arteries with a nonparallel leftward shift in aorta. Verapamil nonsurmountably antagonised contractile responses to 5-HT in aorta and competitively antagonised 5-HT in Tail arteries. Subsequent addition of ketanserin to the verapamil-containing perfusate caused a further shift to the right of the 5-HT dose-response curve in aorta, but had no additional antagonist effect above that of verapamil alone on Tail Artery responses to 5-HT. The results show that although the pharmacological properties of ketanserin and verapamil overlapped, there were marked differences between the pharmacologies of the 5-HT 2A -receptors in the two tissues studied, suggesting either that the mechanism of the 5-HT-induced influx of Ca 2+ is different in the two tissues or that the 5-HT 2A receptors differ structurally between tissues

  • interactions between enalaprilat and doxazosin at rat Tail Artery alpha 1 adrenoceptors
    Journal of Cardiovascular Pharmacology, 1991
    Co-Authors: John F Marwood, Garth Tierney, G S Stokes
    Abstract:

    Using paired isolated perfused rat Tail Artery segments, it was found that enalaprilat, an ACE inhibitor, augmented 1.6-fold the contractile responses to phenylephrine (PE), an alpha 1-adrenoceptor agonist. Similarly, enalaprilat potentiated 1.9-fold the alpha 1-adrenoceptor antagonist activity of doxazosin in paired rat Tail Artery segments. In rats treated with deoxycorticosterone acetate (DOCA) 20 mg/kg i.m. twice weekly for 5 weeks, plasma renin activity fell from a control value of 5.73 +/- 0.93 to 0.04 +/- 0.01 ng of AI/ml/h. The inhibition of circulating renin activity in these animals was associated with a loss of the potentiating effects of enalaprilat upon the alpha 1-adrenoceptor antagonist action of doxazosin. The results are interpreted as indicating that angiotensin II (AII) can modulate the functional activity of alpha 1-adrenoceptors in vascular smooth muscle.

Christine Capdeville-atkinson - One of the best experts on this subject based on the ideXlab platform.

  • Role of Gi-proteins in norepinephrine-mediated vasoconstriction in rat Tail Artery smooth muscle
    Biochemical pharmacology, 2001
    Co-Authors: Marie-anne Petitcolin, Esther Spitzbarth-régrigny, Jean-luc Bueb, Christine Capdeville-atkinson, Eric Tschirhart
    Abstract:

    We showed, in rat de-endothelialised Tail Artery, that pertussis toxin (PTX) (1 μg/mL, 2 hr) attenuated norepinephrine (NE)-induced vasoconstriction without modifying intracellular calcium concentration [Ca2+]i mobilisation. We suggested the existence of two NE-induced intracellular pathways: a first, which would be insensitive to PTX and lead to [Ca2+]i mobilisation, and a second sensitive to PTX and involved in the [Ca2+]i sensitivity of NE-induced contraction. The aim of this study was to demonstrate the existence of the second intracellular pathway. PTX-sensitive Gi/o-proteins in rat Tail Artery SMC membrane were identified by immunoblot and ADP-ribosylation. [32P]ADP-ribosylation of αi/o-subunits was demonstrated in situ by perfusing rat de-endothelialised Tail Artery segments with PTX (1 μg/mL, 2 hr), which suggested that Gi/o-protein inactivation was involved in the reduction by PTX of the [Ca2+]i sensitivity of NE-induced contraction. Coupling between Gi/o-proteins and NE receptors was confirmed by the NE-induced increase in Gi/o-specific GTPase activity (24.1 ± 1.9 vs 8.8 ± 0.4 pmol Pi/mg protein at 5 min; P < 0.05 vs basal). [3H]Prazosin-binding data showed the presence of a heterogeneous α1-AR population in rat Tail Artery smooth muscle cells. We demonstrated the in vitro coupling between α1A-AR subtype and αi-subunits. In conclusion, we identified, in rat de-endothelialised Tail Artery, a PTX-sensitive Gi/o-protein-modulated pathway that is coupled to NE receptors via α1A-AR. We suggest that NE stimulates two α1-AR-mediated intracellular pathways: a first, which is mediated by a Gq-protein and leads to [Ca2+]i mobilisation and contraction, and a second, which is mediated by a Gi-protein and is involved in the amplification of the [Ca2+]i sensitivity of NE-induced tension.

  • Effects of chronic and acute aminoguanidine treatment on Tail Artery vasomotion in ageing rats.
    British journal of pharmacology, 2000
    Co-Authors: Antonia Tabernero, Bruno Corman, Jeffrey Atkinson, Sophie Nadaud, Christine Capdeville-atkinson
    Abstract:

    This study was designed to evaluate the effects of aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), on the reactivity and intracellular calcium ([Ca2+]i) mobilization induced by noradrenaline in the perfused Tail Artery from aged WAG/Rij rats. Global mean internal diameter was 350±15 microns and wall thickness 161±3 microns. The influence of the endothelium on these responses was also analysed. The intracellular dye fura-2 for [Ca2+]i measurements was used. Noradrenaline-induced vasoconstriction decreased progressively from 3 to 20 and 30 months. Removal of the endothelium attenuated vasoconstriction in 20 and 30 month-old rats (P

  • Sympathetic neurotransmission in the Tail Artery of aging rats
    British journal of pharmacology, 1994
    Co-Authors: Eric Thorin, Christine Capdeville-atkinson, Bruno Corman, Jeffrey Atkinson
    Abstract:

    1. Age-related changes in noradrenergic neurotransmission in the Tail arteries of three rat strains: outbred Wistar (WI/Ico), inbred Wistar (WAG/Rij) and inbred Fischer (F344) have been compared in the present study. 2. The arterial noradrenaline content varied from 5 to 10 ng mg-1 wet weight amongst young (3 to 6-month old) representatives of each strain, but did not change with age. As protein content increased in senescent rats (24-month old) by 30-40%, arterial tissue growth would not appear to receive a concomitant increase in sympathetic growth leading to relative, age-related, structural sympathectomy in all strains. 3. The vasoconstrictor response to transmural electrical stimulation was diminished in adult and senescent rats of all strains. 4. As far as could be judged from the increase in noradrenaline release following perfusion with the alpha-adrenoceptor antagonist, phentolamine (1 microM), the presynaptic alpha 2-adrenoceptor-mediated inhibition of noradrenaline release was intact in old representatives of all strains. 5. With blockade of the two main systems which control noradrenaline release in the rat Tail Artery, viz, neuronal reuptake with cocaine (4 microM) and presynaptic alpha 2-adrenoceptors with phentolamine (1 microM), stimulation-evoked release of noradrenaline was similar at all ages and in all strains. This suggests that in the rat Tail Artery the basic mechanism of neuronal release of noradrenaline is not functionally modified by aging. 6 We conclude that as sympathetic nerve terminals are apparently intact in all three strains of senescent rats used, the age-associated deficit of alpha-adrenergic control of vascular function is postsynaptic in nature.

Rui Wang - One of the best experts on this subject based on the ideXlab platform.

  • molecular basis of voltage dependent delayed rectifier k channels in smooth muscle cells from rat Tail Artery
    Life Sciences, 2000
    Co-Authors: Guanghua Tang, Rui Wang
    Abstract:

    Summary The molecular basis of voltage-dependent K + (Kv) current in smooth muscle cells (SMCs) from rat Tail Artery was investigated by screening transcriptional expression of 15 Kv channel α-subunits and 3 Kv β-subunits using RT-PCR technique. Among Kv genes that encode delayed rectifier Kv currents, mRNAs of Kv1.2, Kv1.3, Kv1.5, Kv2.1, Kv2.2, and Kv3.2 were expressed, but those of Kv1.1, Kv1.6, and Kv3.1 were not detected. The transient outward Kv current-encoding genes Kv1.4, Kv3.3, Kv3.4, Kv4.1- Kv4.3 as well as Kvβ1, Kvβ2, and Kvβ3 were also expressed at MRNA level. Western blot study demonstrated the presence of Kv1.2, Kv1.3, Kv1.5, and Kv2.1, but not Kv3.2 proteins, in Tail Artery tissue. Immunocytochemistry study confirmed the presence of Kv1.2, Kv1.3, Kv1.5, and Kv2.1 channel proteins in primary cultured single SMCs. Our results represent the first systematic characterization of Kv gene expression in rat Tail Artery SMCs.

  • Three different vasoactive responses of rat Tail Artery to nicotine.
    Canadian journal of physiology and pharmacology, 2000
    Co-Authors: Rui Wang, Zunzhe Wang
    Abstract:

    The vasoactive effects of nicotine on isolated rat Tail Artery tissues were studied. Nicotine transiently contracted rat Tail Artery tissues (EC50, 55.6 ± 2 µM) in an extracellular Ca2+ dependent and endothelium-independent fashion. The blockade of alpha1-adrenoceptors, but not alpha2-adrenoceptors or P2X purinoceptors, inhibited the nicotine-induced contraction by 38 ± 7% (p =10 mM), triggered a Ca2+-dependent rebound long-lasting vasoconstriction (n = 20). This rebound contraction w...

  • Three different vasoactive responses of rat Tail Artery to nicotine
    Canadian Journal of Physiology and Pharmacology, 1999
    Co-Authors: Rui Wang, Zunzhe Wang
    Abstract:

    The vasoactive effects of nicotine on isolated rat Tail Artery tissues were studied. Nicotine transiently contracted rat Tail Artery tissues (EC50, 55.6 ± 2 µM) in an extracellular Ca2+ dependent and endothelium-independent fashion. The blockade of alpha1-adrenoceptors, but not alpha2-adrenoceptors or P2X purinoceptors, inhibited the nicotine-induced contraction by 38 ± 7% (p < 0.05). Nicotine (1 mM) depolarized membrane by 13 ± 3 mV, but did not affect L-type Ca2+ channel currents, of the isolated rat Tail Artery smooth muscle cells. The phenylephrine-precontracted Tail Artery tissues were relaxed by nicotine (EC50, 0.90 ± 0.31 mM), which was significantly inhibited after the blockade of nicotinic receptors. Simultaneous removal of phenylephrine and nicotine, after a complete relaxation of the phenylephrine-precontracted Tail Artery strips was achieved by nicotine at accumulated concentrations (>=10 mM), triggered a Ca2+-dependent rebound long-lasting vasoconstriction (n = 20). This rebound contraction was abolished in the absence of calcium or in the presence of tetracaine in the bath solution. Pretreatment of vascular tissues with a nicotinic receptor antagonist did not affect the nicotine-induced vasoconstriction or nicotine withdrawal induced rebound contraction. The elucidation of the triphasic vascular effects of nicotine and the underlying mechanisms is important for a better understanding of the complex vascular actions of nicotine.Key words: nicotine, smokeless tobacco, vascular smooth muscles, contraction, relaxation.

  • Altered calcium homeostasis in Tail Artery endothelial cells from spontaneously hypertensive rats
    American Journal of Hypertension, 1995
    Co-Authors: Rui Wang, Rémy Sauvé, Jacques De Champlain
    Abstract:

    Using the fura-2 fluorescence technique, the hypothesis that calcium homeostasis may be altered in vascular endothelial cells of spontaneously hypertensive rats (SHR) was examined. Endothelial cells (EC) were isolated from rat Tail arteries and subcultured for up to three passages. The resting intracellular calcium ion concentration ([Ca 2+ ] i ) in EC from Tail arteries was found to be significantly lower in SHR than that in normotensive WistarKyoto (WKY) rats. Bradykinin and endothelin induced a lesser increase in [Ca 2+ ] i in both the peak increase and the total amount of calcium increase during a defined period of time in Tail Artery EC from SHR, compared with the respective EC from WKY rats. However, there was no significant difference in angiotensin II induced increase in [Ca 2+ ] i in Tail Artery EC between SHR and WKY rats. It is suggested that a lower resting [Ca 2+ ] i and a selectively impaired stimulation-induced increase in [Ca 2+ ] i in EC may contribute to the altered endothelium function in spontaneously hypertensive rats.

Samantha Flanders - One of the best experts on this subject based on the ideXlab platform.

  • mechanisms of melatonin induced vasoconstriction in the rat Tail Artery a paradigm of weak vasoconstriction
    British Journal of Pharmacology, 1999
    Co-Authors: Michael J. Lew, Samantha Flanders
    Abstract:

    Vasoconstrictor effects of melatonin were examined in isolated rat Tail arteries mounted either in an isometric myograph or as cannulated pressurized segments. Melatonin failed by itself to mediate observable responses but preactivation of the arteries with vasopressin (AVP) reliably uncovered vasoconstriction responses to melatonin with maxima about 50% of maximum contraction. Further experiments were conducted with AVP preactivation to 5–10% of the maximum contraction. Responses to melatonin consisted of steady contractions with superimposed oscillations which were large and irregular in isometric but small in isobaric preparations. Nifedipine (0.3 μM) reduced the responses and abolished the oscillations. Charybdotoxin (30 nM) increased the magnitude of the oscillations with no change in the maximum response. Forskolin (0.6 μM) pretreatment increased the responses to melatonin compared to control and sodium nitroprusside (1 μM) treated tissues. The AVP concentration required for preactivation was 10 fold higher than control in both the forskolin and nitroprusside treated groups. In isometrically-mounted arteries treated with nifedipine, melatonin receptor agonists had the potency order 2-iodomelatonin>melatonin>{"type":"entrez-protein","attrs":{"text":"S20098","term_id":"100417","term_text":"pir||S20098"}}S20098>{"type":"entrez-nucleotide","attrs":{"text":"GR196429","term_id":"238463753","term_text":"GR196429"}}GR196429, and the MT2-selective antagonist luzindole antagonized the effects of melatonin with a low pKB of 6.1±0.1. It is concluded that melatonin elicits contraction of the rat Tail Artery via an mt1 or mt1-like receptor that couples via inhibition of adenylate cyclase and opening of L-type calcium channels. Calcium channels and charybdotoxin-sensitive K+ channels may be recruited into the responses via myogenic activation rather than being coupled directly to the melatonin receptors. It is proposed that the requirement of preactivation for overt vasoconstrictor responses to melatonin results from the low effector reserve of the melatonin receptors together with the Tail Artery having threshold inertia. Potentiative interactions between melatonin and other vasoconstrictor stimuli probably also result from the threshold inertia. A simple model is presented and a general framework for consideration of interactions between weak vasoconstrictor agonists and other vasoconstrictor stimuli is discussed. Keywords: Melatonin, mt1 receptors, MEL1 receptors, cyclic AMP, potentiation, vasoconstriction, preactivation, rat Tail Artery Introduction Vascular melatonin receptors have been identified by specific 2-[125I]-iodomelatonin binding in rat Tail and cerebral vessels (Capsoni et al., 1994; Seltzer et al., 1992; Viswanathan et al., 1990; 1992; 1993) as well as in cerebral vessels from primates, including humans, (Stankov et al., 1993; Stankov & Fraschini, 1993). The vasoactive effects of melatonin have best been described in the rat Tail Artery where it has been shown to potentiate contractile responses of noradrenaline and sympathetic nerve stimulation (Krause et al., 1995; Ting et al., 1997; Viswanathan et al., 1990). However, direct smooth muscle contractions to melatonin have proved difficult to detect. For example, melatonin failed to cause contractions in arteries studied under isometric conditions (Krause et al., 1995; Viswanathan et al., 1990) while in pressurized arteries vasoconstriction occurred in only a minority of the tissues examined (Evans et al., 1992; Ting et al., 1997). The unreliability of vasoconstrictor responses to melatonin in the Tail Artery has not been adequately explained, particularly in light of the fact that melatonin seems to always enhance the responses to sympathetic nerve stimulation in that tissue. We noted that in all cases where melatonin mediated vasoconstriction the maximum effect of melatonin was small compared to noradrenaline, and thus we would classify melatonin vascular receptors as a weak vasoconstrictor system. We have previously found that slight preactivation of rat mesenteric arteries exposes otherwise invisible vasoconstriction responses to neuropeptide Y, an agonist that also has a small maximum effect compared to noradrenaline in most tissues (Lew et al., 1996). Thus the intention of this study was to determine whether preactivation could expose vasoconstrictor responses to melatonin in wire-mounted (isometric) and pressurized (isobaric) segments of rat Tail Artery and to characterize any responses obtained. The results led us to conclude that stimulus-response coupling pathways are stimulated both directly and indirectly during the responses to melatonin, and that the vasoconstrictor and potentiative effects of melatonin are the same. In those respects melatonin appears no different to other weak vasoconstrictor agonists that act at other receptor types. We propose a hypothesis about differences in the behaviours of weak and strong vasoconstrictor systems that appears to be generally applicable and predicts many of the patterns of interaction that have been previously reported as notable.

  • Mechanisms of melatonin‐induced vasoconstriction in the rat Tail Artery: a paradigm of weak vasoconstriction
    British journal of pharmacology, 1999
    Co-Authors: Michael J. Lew, Samantha Flanders
    Abstract:

    Vasoconstrictor effects of melatonin were examined in isolated rat Tail arteries mounted either in an isometric myograph or as cannulated pressurized segments. Melatonin failed by itself to mediate observable responses but preactivation of the arteries with vasopressin (AVP) reliably uncovered vasoconstriction responses to melatonin with maxima about 50% of maximum contraction. Further experiments were conducted with AVP preactivation to 5–10% of the maximum contraction. Responses to melatonin consisted of steady contractions with superimposed oscillations which were large and irregular in isometric but small in isobaric preparations. Nifedipine (0.3 μM) reduced the responses and abolished the oscillations. Charybdotoxin (30 nM) increased the magnitude of the oscillations with no change in the maximum response. Forskolin (0.6 μM) pretreatment increased the responses to melatonin compared to control and sodium nitroprusside (1 μM) treated tissues. The AVP concentration required for preactivation was 10 fold higher than control in both the forskolin and nitroprusside treated groups. In isometrically-mounted arteries treated with nifedipine, melatonin receptor agonists had the potency order 2-iodomelatonin>melatonin>{"type":"entrez-protein","attrs":{"text":"S20098","term_id":"100417","term_text":"pir||S20098"}}S20098>{"type":"entrez-nucleotide","attrs":{"text":"GR196429","term_id":"238463753","term_text":"GR196429"}}GR196429, and the MT2-selective antagonist luzindole antagonized the effects of melatonin with a low pKB of 6.1±0.1. It is concluded that melatonin elicits contraction of the rat Tail Artery via an mt1 or mt1-like receptor that couples via inhibition of adenylate cyclase and opening of L-type calcium channels. Calcium channels and charybdotoxin-sensitive K+ channels may be recruited into the responses via myogenic activation rather than being coupled directly to the melatonin receptors. It is proposed that the requirement of preactivation for overt vasoconstrictor responses to melatonin results from the low effector reserve of the melatonin receptors together with the Tail Artery having threshold inertia. Potentiative interactions between melatonin and other vasoconstrictor stimuli probably also result from the threshold inertia. A simple model is presented and a general framework for consideration of interactions between weak vasoconstrictor agonists and other vasoconstrictor stimuli is discussed. Keywords: Melatonin, mt1 receptors, MEL1 receptors, cyclic AMP, potentiation, vasoconstriction, preactivation, rat Tail Artery Introduction Vascular melatonin receptors have been identified by specific 2-[125I]-iodomelatonin binding in rat Tail and cerebral vessels (Capsoni et al., 1994; Seltzer et al., 1992; Viswanathan et al., 1990; 1992; 1993) as well as in cerebral vessels from primates, including humans, (Stankov et al., 1993; Stankov & Fraschini, 1993). The vasoactive effects of melatonin have best been described in the rat Tail Artery where it has been shown to potentiate contractile responses of noradrenaline and sympathetic nerve stimulation (Krause et al., 1995; Ting et al., 1997; Viswanathan et al., 1990). However, direct smooth muscle contractions to melatonin have proved difficult to detect. For example, melatonin failed to cause contractions in arteries studied under isometric conditions (Krause et al., 1995; Viswanathan et al., 1990) while in pressurized arteries vasoconstriction occurred in only a minority of the tissues examined (Evans et al., 1992; Ting et al., 1997). The unreliability of vasoconstrictor responses to melatonin in the Tail Artery has not been adequately explained, particularly in light of the fact that melatonin seems to always enhance the responses to sympathetic nerve stimulation in that tissue. We noted that in all cases where melatonin mediated vasoconstriction the maximum effect of melatonin was small compared to noradrenaline, and thus we would classify melatonin vascular receptors as a weak vasoconstrictor system. We have previously found that slight preactivation of rat mesenteric arteries exposes otherwise invisible vasoconstriction responses to neuropeptide Y, an agonist that also has a small maximum effect compared to noradrenaline in most tissues (Lew et al., 1996). Thus the intention of this study was to determine whether preactivation could expose vasoconstrictor responses to melatonin in wire-mounted (isometric) and pressurized (isobaric) segments of rat Tail Artery and to characterize any responses obtained. The results led us to conclude that stimulus-response coupling pathways are stimulated both directly and indirectly during the responses to melatonin, and that the vasoconstrictor and potentiative effects of melatonin are the same. In those respects melatonin appears no different to other weak vasoconstrictor agonists that act at other receptor types. We propose a hypothesis about differences in the behaviours of weak and strong vasoconstrictor systems that appears to be generally applicable and predicts many of the patterns of interaction that have been previously reported as notable.