UCL University College London Eprints
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Inhibition of norepinephrine and caffeine-induced activation by ryanodine and thapsigargin in rat mesenteric arteries. - Garcha, RS; Hughes, AD
We examined the effects of ryanodine and thapsigargin on changes in cytoplasmic [Ca2+] (Cai) and muscle tension in rat mesenteric resistance arteries induced by norepinephrine (NE) and caffeine. Both ryanodine and thapsigargin markedly inhibited the increase in Cai and contractile responses to caffeine in physiological saline and to NE and caffeine in calcium-free conditions. In contrast, peak responses to potassium depolarisation and NE in physiological saline appeared little affected, although time taken to achieve 50% of peak response after addition of NE was slowed after ryanodine and thapsigargin treatment. Neither ryanodine nor thapsigargin altered resting tone or Cai or the...
Effect of platelet-derived growth factor on voltage-operated calcium channels in rabbit isolated ear artery cells. - Wijetunge, S; Hughes, AD
1. Platelet derived growth factor (PDGF), AB and BB isoforms (100 pM) increased calcium channel currents measured by whole cell voltage clamp technique in single vascular smooth muscle cells isolated from rabbit ear arteries. 2. Tyrphostin-23 (100 microM) a selective inhibitor of protein tyrosine kinases, reduced calcium channel currents. Pre-incubation with tyrphostin-23 prevented PDGF-AB induced increase in calcium channel currents. However, in these same cells 10 nM (+)-202791, a dihydropyridine calcium channel agonist, did increase calcium channel currents. 3. Bistyrphostin (10 microM), a selective inhibitor of epidermal growth factor (EGF)-kinase also reduced calcium channel currents and inhibited PDGF-AB-induced increases in...
The mechanism of action of alpha 2-adrenoceptors in human isolated subcutaneous resistance arteries. - Parkinson, NA; Hughes, AD
1. The effect of noradrenaline and the selective alpha 2-adrenoceptor agonist, azepexole, on tone and intracellular Ca2+ ([Ca2+]i) was examined in human isolated subcutaneous resistance arteries. Isolated arteries were mounted on an isometric myograph and loaded with the Ca2+ indicator, fura-2, for simultaneous measurement of force and [Ca2+]i. 2. High potassium solution (KPSS), noradrenaline and azepexole increased [Ca2+]i and contracted subcutaneous arteries in physiological saline. When extracellular Ca2+ was removed and the calcium chelator, BAPTA, added to the physiological saline (PSSo), responses to noradrenaline were transient and reduced, and responses to azepexole were markedly inhibited. 3. Ryanodine, an agent which...
Action of angiotensin II, 5-hydroxytryptamine and adenosine triphosphate on ionic currents in single ear artery cells of the rabbit. - Hughes, AD; Bolton, TB
1. Angiotensin II, 5-hydroxytryptamine (5-HT) and adenosine triphosphate (ATP) evoked a transient inward current in isolated single car artery cells of rabbit held at -60 mV by whole cell voltage clamp in physiological saline using a KCL-containing pipette solution. Under these conditions agonist did not activate a calcium-dependent potassium current. 2. Responses to each agonist were transient and desensitized rapidly. Inward current at -60 mV holding potential was not abolished by blockade of voltage-dependent calcium channels or by buffering intracellular calcium with BAPTA, a calcium chelator, or following depletion of intracellular calcium stores with ryanodine. 3. The shape of the...
Calcium channels in vascular smooth muscle cells. - Hughes, AD
Control of intracellular Ca2+ ([Ca2+]i) is critical to vascular smooth muscle function. Calcium channels are the major route by which Ca2+ enters the smooth muscle cell. This article reviews the types of calcium channel present in vascular smooth muscle cells and their physiological and biochemical regulation.
pp60c-src increases voltage-operated calcium channel currents in vascular smooth muscle cells. - Wijetunge, S; Hughes, AD
Intracellular application of pp60c-src, a nonreceptor tyrosine kinase present in large amounts in smooth muscle cells increased voltage-operated calcium channel currents in rabbit ear artery cells. Intracellular peptide-A, an inhibitor of pp60c-src, reduced calcium channel currents and abolished the action of pp60c-src. Selective tyrosine kinase inhibitors, tyrphostin-23 and genistein also abolished the effect of pp60c-src, but inhibition of protein kinase C did not prevent the action of pp60c-src. These results suggest that endogenous pp60c-src modulates voltage-operated calcium channels by a mechanism dependent on tyrosine phosphorylation but not involving activation of protein kinase C.
Action of losartan, PD-123,319 and endothelial factors on angiotensin-II (AU) responses in human resistance arteries - Garcha, RS; Schachter, M; Sever, PS; Hughes, AD
Mammalian All receptors have been classified as AT, and AT; subtypes. Losartan is the archetypal non-peptide AT] receptor antagonist and PD-123,319 is an AT: specific receptor antagonist. The aim of ihis study was to examine ihe contribution oi AT and AT receptor subtypes and possible influence of endolhelial-derived factoron All-induced contraction in isolated human subcutaneous resistance arteries Human subcutaneous resistance arteries (diameter
α-Adrenoceptor activation increases calcium channel currents in single vascular smooth muscle cells isolated from human omental resistance arteries - Hughes, AD; Parkinson, NA; Wijetunge, S
Single cells were freshly isolated from human omental resistance arteries using an enzymatic dispersion technique. Calcium channel currents (I(Ba)) were recorded using whole cell voltage clamp techniques with Ba as the charge carrier. BHT 933, a selective α-adrenoceptor agonist, increased I(Ba). The effect of BHT 933 was reversible following washout. The action of BHT 933 was blocked by yohimbine. Pretreatment of tissues with pertussis toxin for 18 h or inclusion of GDP-β-S in the intracellular patch pipette solution also prevented the BHT 933-induced rise in I(Ba), but had no effect on I(Ba) in the absence of BHT 933. Activation of...
Enhanced tissue polyamine content in the spontaneously hypertensive rat. - Ibrahim, J; Hughes, AD; Schachter, M; Sever, PS
1. Endogenous polyamines play a key role in mediating cellular growth and differentiation. Hypertension is associated with structural modifications of the circulatory system, a process that may be facilitated by polyamines. In this study, we examined whether there are elevated polyamine concentrations in the cardiovascular tissues of spontaneously hypertensive rats (SHR) relative to Wistar-Kyoto (WKY) rats. We also determined the chronic effect of 2% difluoromethylornithine (DFMO; a polyamine biosynthesis inhibitor) on tissue polyamines and hypertension. 2. SHR and WKY rats were treated with either 2% DFMO or drug-free drinking water; blood pressure was measured on alternate days and tissue polyamines...
Platelet-derived growth factor (PDGF): actions and mechanisms in vascular smooth muscle. - Hughes, AD; Clunn, GF; Refson, J; Demoliou-Mason, C
1. PDGF is a highly hydrophilic cationic glycoprotein (M(r) 28-35kDa) produced by platelets, monocyte/macrophages, endothelial cells and vascular smooth muscle cells under some conditions. 2. Since its original description, PDGF has attracted much attention and it is currently believed to play a role in atherosclerosis and other vascular pathologies. 3. This review describes the vascular biology of PDGF. It particularly focuses on recent findings regarding the intracellular signals activated by PDGF in the context of vascular smooth muscle cell proliferation, migration and, contraction.
Depletion of resistance vessel polyamines attenuates angiotensin II induced blood pressure rise in rats. - Ibrahim, J; Hughes, AD; Schachter, M; Sever, PS
Vascular structural changes in hypertension are proposed to contribute to raised peripheral resistance. Endogenous polyamines (putrescine, spermidine and spermine) have an essential role in cellular growth and may be required in vascular restructuring. We have previously shown raised polyamines in resistance vessels in response to angiotensin II (angII) infusion in the rat and here we examined whether polyamine depletion influences the hypertensive process. Wistar-Kyoto rats were infused with either angII or saline by osmotic minipump, and maintained on either 2% difluoromethylornithine (DFMO; polyamine synthesis inhibitor) or water for 12 days. AngII significantly increased tail-cuff blood pressure (bp), resistance vessel spermidine...