Biomedical subjects

Y Y Guan

Publications and source records attributed to Y Y Guan.

At least 19 recordsLinked to original sources

PubMed2001

Contractile responses of diabetic rat aorta to phenylephrine at different stages of diabetic duration.

AIM: To investigate the time-dependent changes in contractile responses of aorta to phenylephrine (Phe) in diabetic rats and age-matched control, and its possible mechanism. METHODS: At stages of 2-, 6-, and 12-week diabetic duration, aortic rings were studied for contractile responses to agonists in vitro. RESULTS: At the stage of 2-week diabetic duration, contractile responses to lower concentrations of phenylephrine were increased (P < 0.05), but the maximal contraction of phenylephrine did not change. At the stage of 6-week diabetic duration, contractile responses to phenylephrine were increased (P < 0.01) at each concentration, and the maximal contraction was increased by approximately 40 %. However, at the stage of 12-week diabetic duration: 1) the maximal contractile response to Phe 10 micromol . L-1 was decreased (P < 0.05), 2) in Ca2+ free edetic acid medium, Phe 10 micromol . L-1-induced transient contraction was also decreased (P < 0.05), 3) in Ca2+ free edetic acid medium, in the presence of nifedipine 10 micromol . L-1 and Phe 10 micromol . L-1, the Ca2+ repletion-caused contraction was not different from control, 4) in normal medium, cyclopiazonic acid (CPA) 10 micromol . L-1-induced contraction was decreased (P < 0.01). CONCLUSION: The results suggested that contractile responses to phenylephrine in diabetic rat aorta changed with the development of diabetes, and the changes of functional Ca2+ store sizes and Ca2+ entry mainly through voltage-dependent Ca2+ channels were responsible for the alterations of contractile responses to phenylephrine in diabetes.

Adrenergic alpha-Agonists↗

PubMed2000

Effects of Scutellarein on diabetic rat aorta.

AIM: To study the effect of Scutellarein (Scu) on the diabetic rat aorta. METHODS: Contractile responses to phenylepherine and endothelium-dependent relaxation responses to acetylcholine (ACh) in rat aorta were investigated after streptozocin-induced 6-wk diabetes, Scu-treated streptozocin-induced diabetes, and in age-matched control in vitro. RESULTS: 1) Endothelium-dependent relaxation to ACh in diabetic rats was decreased (P < 0.01) compared with age-matched control. 2) Contractile responses to phenylepherine were increased (P < 0.01) in diabetic rats. 3) The dietary supplement of 0.5% Scu starting from 1-wk diabetes induction prevented endothelial dysfunction (P < 0.01), but the contractile responses to phenylepherine were further increased. CONCLUSION: Scu prevented vascular endothelial dysfunction in diabetic rats, and also potentiated the contraction induced by phenylepherine.

Animals↗

PubMed1999

Erigeron breviscapus prevents defective endothelium-dependent relaxation in diabetic rat aorta.

We examined the endothelium-dependent relaxation response to acetylcholine (Ach) in streptozotocin-induced diabetic rat aorta at the stages of 2- and 6-wks' duration in vitro, and compared with another two groups which were treated with dietary supplement of 0.1% Aminoquanidine (AG) and 0.5% Erigeron breviscapus (EB) from 1-week of diabetes induction. At the stage of 2-wks' duration of diabetes, relaxation responses to lower concentrations of Ach in 0.3 uM phenylepherine-precontracted aortas were diminished significantly (P<0.05) compared with age-matched control, but the maximal relaxation of Ach remained unchanged. At the stage of 6-wks' duration, diabetes caused an approximately 60% (P<0.001) deficit in maximum relaxation, and this was significantly (P<0.001) prevented in AG and EB treated groups. There was an approximately 40% enhancement in the maximum contractile response to phenylepherine with diabetes (P<0.05), which was unaffected significantly by AG and EB treatments. The data suggest that the defective endothelium-dependent relaxation in diabetic rat aorta occurred as early as 2-wks' duration of diabetes, and the treatments of AG and EB could protect vascular endothelium although the deficits in vascular smooth muscle contractile responses were not protected.

Acetylcholine↗

PubMed1998

Effects of erythrocyte lysate of different incubation times on intracellular free calcium in rat basilar artery smooth-muscle cells.

OBJECT: The purpose of this study was to characterize substance(s) in the erythrocytes that increase intracellular free Ca++ concentration ([Ca++]i) in smooth-muscle cells and that therefore may be involved in the pathogenesis of vasospasm. METHODS: Because vasospasm occurs days after subarachnoid hemorrhage (SAH), the authors studied the effects of aged human erythrocyte hemolysate and its low-molecular-weight (LMW) and high-molecular-weight (HMW) fractions on [Ca++]i in freshly isolated rat basilar artery smooth-muscle cells. Fresh hemolysate (Day 0) produced a biphasic response consisting of a transient peak and a sustained plateau increase in [Ca++]i, whereas hemolysate prepared from cells incubated for 3, 7, or 14 days induced only a transient response without a sustained phase. The effect of hemolysate declined with increasing incubation time. The HMW fraction and purified human oxyhemoglobin (OxyHb) did not evoke a response. The LMW fraction from Days 3, 7, or 14 produced no response at low concentrations (< 10%) and a transient response at high concentrations (> 20%), and the effect diminished with increasing incubation time. Unfractionated hemolysate or the LMW fraction of hemolysate incubated for 21 days produced no response. The combination of the 10% LMW fraction from Day 3 plus the 10% HMW fraction (Days 3. 7, 14, or 21) transiently increased [Ca++]i,. However, [Ca++]i was not changed by the 10% LMW fraction from Day 14 plus the 10% HMW fraction from Day 3 or 14. In the presence of OxyHb, [Ca++]i was increased by the 10% LMW fraction on Days 3 and 7, but not by the LMW fraction from Days 14 or 21. CONCLUSIONS: The decline over time in the effect of hemolysate on [Ca++]i indicates either that the time that substances are released from erythrocytes is important in the generation of vasospasm or that this experimental system as used is not representative of conditions present after SAH. The data indicate that the ability to elevate [Ca++]i in smooth-muscle cells with hemolysate is provided by multiple substances, including OxyHb. These substances may interact during specific times after incubation of erythrocytes in vitro.

Animals↗

PubMed1997

Comparison of the Ca2+ movement by activation of alpha1-adrenoceptor subtypes in HEK-293 cells.

We studied the Ca2+ movement induced by activation of alpha1A-, alpha1B- and alpha1D-adrenoceptor subtypes in transfected HEK-293 cells with the fura-2 probe. All these alpha1-AR subtypes induced both Ca2+ release and Ca2+ entry. The effect on Ca2+ release in alpha1b transfected HEK-293 cells was bigger than that in alpha1a and alpha1d transfected HEK-293 cells, and the effects on Ca2+ entry were the same in alpha1a, alpha1b and alpha1d transfected HEK-293 cells. The Ca2+ entry was inhibited by 1 mM NiSO4, but not by nifedipine. Cyclopiazonic acid (CPA) produced a biphasic Ca2+ signal response in Ca2+ medium, and only induced a transient response in Ca2+-free medium. After depletion of CPA-sensitive Ca2+ pool by 10 microM CPA in Ca2+-free medium, 10 microM adrenaline (Adr) still transiently increased [Ca2+]i in three different alpha1-adrenoceptor subtype transfected HEK-293 cells. However, after depletion of adrenaline-sensitive Ca2+ pool by 10 microM Adr, CPA transiently elevated [Ca2+]i only in alpha1a and alpha1d transfected HEK-293 cells, not in alpha1b transfected HEK-293 cells. U73122, a phospholipase C (PLC) inhibitor, inhibited both Ca2+ release and Ca2+ entry induced by activation of alpha1A alpha1B and alpha1D subtypes in transfected HEK-293 cells. These results suggest that HEK-293 cell line contains two functionally separate intracellular Ca2+ pools, CPA-sensitive and Adr-sensitive pools. Activation of alpha1B-AR stimulates Ca2+ release from both CPA-sensitive and Adr-sensitive Ca2+ pools. Alpha1A and alpha1D subtypes induce Ca2+ release only from Adr-sensitive Ca2+ pool.

Animals↗

PubMed1996

In vitro inhibitory effects of chebulinic acid on the contractile responses of cardiovascular muscles.

1. The effects of chebulinic acid, which has been shown to elicit blood pressure lowering effect in rats, on aortic vascular contraction as well as cardiac contraction were studied in rats. 2. Chebulinic acid had no effect on KCl-induced aortic contraction, but irreversibly inhibited the contractile responses to phenylephrine in an apparently non-competitive manner. Chebulinic acid also inhibited contractile responses of rat aorta to 5-hydroxytryptamine and angiotensin II. 3. Chebulinic acid inhibited the binding of [3H]-prazosin to dog aortic microsomal membranes in a concentration-dependent manner with an IC50 value of 0.34 mmol/L. Results of saturation binding experiments suggest a mixed mode of inhibition by chebulinic acid (i.e. a decrease in both the maximal number of binding sites and the affinity for prazosin). 4. Chebulinic acid concentration-dependently and reversibly inhibited the maximal left ventricular pressure of rat heart in a Langendorff preparation with 50% inhibition occurring at a concentration of 0.3 nmol/L. 5. We conclude that chebulinic acid exerts non-specific inhibitory actions in vascular preparations. Its inhibitory effect on cardiac contraction was reversible and three orders of magnitude more potent than that on vascular contraction. We suggest that the hypotensive effect of chebulinic acid is probably mediated via the decrease in cardiac output resulting from reduced left ventricular contraction.

Adrenergic alpha-Antagonists↗

PubMed1996

Two-state stochastic models for memory in ion channels.

AIM: To study quantitatively the memory existing in ion channels. METHODS: Stochastic processes were used to model 2 categories of memory (short-term and long-term) by persisting in the standpoint of two-state, instead of multiple states, but with different transition mechanism. RESULTS: A two-state Markov process with constant transition intensities well fitted the short-term memory and a two-state Markov process within a kind of random environment well fitted the long-term memory. Statistical procedures for parameter estimation were proposed and demonstrated with 2 real examples on the channels of PC12 cells. CONCLUSION: The memory in ion channels can be quantitatively modelled as stochastic process with 2 states.

Adrenal Gland Neoplasms↗

PubMed1995

Existence of memory in ion channels.

AIM: To explore the existence of memory in Ca(2+)-dependent K+ channels of cultured aortic smooth muscle cells (ASMC) and voltage-dependent K+ channels of clonal pheochromocytoma (PC12) cells. METHODS: Calculating the sample auto-correlation functions based on the digitized signals or the 0-1 series corresponding to closing and opening of the channels after routine evaluation, rather than the sequence of sojourn times. RESULTS: The sample auto-correlations showed a decreasing trend with elapse of time, stable to repeated observations under the same conditions and sensitive to treatments. CONCLUSION: The attribute of memory exists in some single channels as an intrinsic feature of them, independent of any extrinsic assumptions on missing observations due to limited time resolution.

Animals↗

PubMed1994

Effects of Panax notoginseng saponins on receptor-operated Ca2+ channels in vascular smooth muscle.

The effects of saponins of Panax notoginseng (PNGS) on the alpha-adrenoceptor agonists-induced contractile responses and Ca2+ movement were studied in dog mesenteric artery (MA) and saphenous vein (SV). PNGS reduced the contractions and the 45Ca influx (from 0.36 +/- 0.03 to 0.14 +/- 0.05 mumol.g-1 wet strip) induced by phenylephrine (Phe) without effect on KCl-induced contraction and 45Ca influx which were nearly completely inhibited by nifedipine 0.1 mumol.L-1. PNGS did not change the 45Ca efflux induced by Phe and the Kd value (from 0.76 +/- 0.04 to 0.72 +/- 0.15 nmol.L-1) for [3H]prazosin binding on the microsomal membrane isolated from MA. Our results indicate that PNGS selectively inhibits Ca2+ entry through receptor-operated Ca2+ channel.

Adrenergic alpha-Agonists↗

PubMed1993

Effects of direct lytic factors from southern Chinese cobra venom on Ca2+ movement in rabbit aorta strip.

The purified direct lytic factors (DLF) from southern Chinese cobra (Naja naja atra) venom induced a contractile response in Ca(2+)-free Krebs' solution and a further increase in the tension following a subsequent addition of Ca2+ into bath. After depletion of intracellular Ca2+ pool by phenylephrine, DLF failed to induce any contractile response. In 45Ca2+ experiments, DLF increased both 45Ca2+ release and 45Ca2+ influx. Procaine 2 mmol.L-1 decreased the DLF induced 45Ca2+ release and 45Ca2+ influx by 67 +/- 23% and 46 +/- 32%, respectively. Nifedipine and verapamil 1 mmol.L-1 markedly inhibited the contractile response and the 45Ca2+ influx induced by DLF. These results suggest that DLF induces extracellular Ca2+ entry through voltage dependent Ca2+ channel and Ca2+ release from the intracellular Ca2+ pool which is sensitive to phenylephrine.

Animals↗

PubMed1993

Cyclopiazonic acid causes endothelium-dependent relaxation in rat aorta.

The effects of cyclopiazonic acid (CPA), a selective inhibitor of Ca(2+)-pump ATPase for endoplasmic reticulum (ER), on the contractility of rat aorta with and without intact endothelium were studied to investigate the possible involvement of endothelial ER Ca(2+)-pump in the release of endothelium-derived relaxing factor (EDRF), which is known to cause vascular relaxation or inhibition of phenylephrine (PE)-precontracted aorta. When added to the organ bath cumulatively, CPA concentration-dependently caused gradual development of contraction, which was much less in aortic rings with intact endothelium than in endothelium-denuded aortic rings. But CPA at low concentrations (1-3 mumol.L-1) induced vascular relaxation when added to PE (3 mumol.L-1)-precontracted aortic rings with intact endothelium, but not in denuded aortic rings. This relaxant effect of CPA is very similar to the effect of acetylcholine (ACh), which is well recognized to be mediated by the release of EDRF from the endothelium. NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, completely prevented the vascular relaxation induced by CPA or ACh and the inhibitory effect of L-NAME was partially reversed by L-arginine (L-Arg). Treatment of the aortic rings with nifedipine (Nif) 0.3 mumol.L-1 did not affect the relaxant effect of ACh or CPA on PE-induced contraction indicating that the Ca(2+)-entry to the endothelial cells as a result of receptor activation by ACh or ER Ca(2+)-pump inhibition by CPA was via channels other than L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1992

The relation between transmitter release and Ca2+ entry at the mouse motor nerve terminal: role of stochastic factors causing heterogeneity.

The relation between quantal transmitter release and presynaptic Ca2+/Ba2+ entry at the mouse neuromuscular junction was studied, making use of the finding that in the presence of Ba2+ trains of nerve stimuli or brief nerve terminal depolarizations elicit "tails" of raised miniature end-plate potential frequency (fm) that reflect entry of Ba2+ per pulse, and hence effectiveness of pulses in opening Ca2+/Ba2+ channels; at the same time these pulses elicit end-plate potentials. With nerve stimulation in the presence of Ba2+ and Ca2+ and modulation of release by raised Mg2+ or bekanamycin, slopes of log quantal content (m) vs log apparent Ba2+ entry per pulse were close to 4, which is the same as the Hill coefficient for Ba2+ cooperativity derived from other data. With depolarizing pulses of varied intensity, however, similar plots gave slopes close to 2, with Ba2+ alone or in a mixture of Ca2+ and Ba2+. Thus, the relation between transmitter release and Ca2+ (or Ba2+) entry apparently depends upon how entry is varied; varying the numbers of channels opened is not the same as varying ion entry per channel. A mathematical model was developed to examine the consequences of heterogeneity of local Ca2+ (or Ba2+) between release sites, arising because of stochastic variation of number and time course of Ca2+ channels opened per site; the experimental results were consistent with this model. It was therefore concluded that release is normally governed by intracellular Ca2+ close to points of Ca2+ entry through channels; stochastic factors give rise to more release than if Ca2+ were homogeneously distributed. If Ca2+ channels are uniformly close to release sites the average number of channels opened per site per action potential may be as low as 4.

Animals↗

PubMed1992

The effect of neonatal treatment of rats with nerve growth factor on the blood pressure and structure of the mesenteric arteries.

Newborn male Wistar rats were treated with nerve growth factor daily by subcutaneous injection for 2 weeks, and control rats were treated with either cytochrome c or buffered saline. Average body weight of the treated animals was lower than that of the controls during the 2 weeks of treatment, but became similar to that of the controls thereafter. Tissue levels of norepinephrine were elevated in the brain, adrenal glands, mesenteric arteries, and vas deferens of the treated animals immediately after the treatment, but became similar in the three groups 2 weeks after the termination of the treatment. Blood pressure and heart rate were measured beginning at 4 weeks of age until 28 weeks, when the rats were sacrificed and the mesenteric arteries sampled for morphometric measurements of vessel wall dimensions. Pretreatment with nerve growth factor did not affect blood pressure, nor heart rate. Structural alteration of the three types of mesenteric arteries was also absent in the treated animals. We conclude that even though neonatal treatment of normal Wistar rats with nerve growth factor for 2 weeks induced an elevation of the norepinephrine levels in several tissues at the end of the treatment period, it was not sufficient to produce hypertension and structural alterations in the blood vessels.

Aging↗

PubMed1992

Tetrandrine is not a selective calcium channel blocker in vascular smooth muscle.

The effects of tetrandrine (Tet) on the contractile properties of rat aortic ring preparations were studied to test the hypothesis that Tet is a Ca2+ antagonist acting on voltage-operated Ca2+ channels (VOC). The tests were performed on contractions induced by depolarizing concentrations of KCl and by alpha 1-adrenoceptor agonist, phenylephrine (Phe). These vascular effects of Tet were compared to those of nifedipine (Nif). We found that Tet behaved qualitatively similar to, but less potent than, Nif in that it inhibited KCl-induced contraction in a concentration-dependent fashion and its inhibitory effect was long-lasting. However, the effects on Phe-induced contraction of Tet was different from those of Nif in that the extracellular Ca(2+)-dependent contraction was inhibited by Tet, but not by Nif. Tet (60 mumol.L-1) completely inhibited the 45Ca2+ uptake induced by KCl and Phe in rat aortic muscle strips. When the aortic muscle contractile response was induced by addition of Ca2+ following depletion of intracellular stores by Phe in the presence of sarcoplasmic reticulum Ca(2+)-pump inhibitor, cyclopiazonic acid, Tet (60 mumol.L-1) was more effective than Nif 1 mumol.L-1 in inhibiting such a response to extracellularly added Ca2+. Furthermore, Tet, but not Nif, also significantly inhibited the contraction to Phe in Ca(2+)-free medium. Collectively, these results led us to conclude that Tet does not behave as a selective VOC blocker like Nif.

Alkaloids↗

PubMed1991

Alpha 1-adrenoceptors mediate the responses to BHT-920 and rauwolscine in dog mesenteric artery after partial depolarization by KCl.

In normal (5 mM KCl) HEPES buffer solution, BHT-920 and rauwloscine did not produce any contractile responses in dog mesenteric artery strips. However, when the preparation was bathed in 20 mM KCl HEPES buffer solution, BHT-920 and rauwloscine evoked significant contractile responses. These effects were markedly inhibited by parazosin which caused a parallel shift to the right of the concentration-response curve to BHT-920. In 45Ca uptake experiments carried out in the 20 mM KCl HEPES buffer solution BHT-920 and rauwolscine significantly increased 45Ca influxes which were reduced by prazosin. These results suggest that postsynaptic alpha 1-adrenoceptors in dog mesenteric artery mediate the contractile responses and the 45Ca influxes induced by BHT-920 and rauwloscine after partial depolarization by 20 mM KCl.

Adrenergic alpha-Agonists↗

PubMed1991

Contractile response of aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium is reduced in spontaneous hypertension.

Vascular responses of aortic rings to alpha 1-adrenergic stimulation by phenylephrine (Phe) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were studied in Ca(2+)-containing medium and Ca(2+)-free medium plus 50 mumol/L EGTA. Although there was no difference in the sustained force development between SHR and WKY vessels in response to 100 mmol/L KCl or 10 mumol/L Phe in Ca(2+)-containing medium, the transient contractile response to 10 mumol/L Phe in Ca(2+)-free medium was substantially smaller in SHR compared to that in WKY. Subsequent addition of 2.5 mmol/L Ca2+ restored the sustained contractile response to a similar level in both SHR and WKY vessels. The transient contractile response to Phe in Ca(2+)-free medium containing EGTA, presumably due to the release of intracellular Ca2+, decreased progressively with preincubation time in Ca(2+)-free medium, indicating intracellular Ca2+ depletion. Such a temporal change of aortic response was more pronounced in SHR than in WKY. The subsequent response to Ca2+ repletion in the presence of Phe, on the other hand, increased progressively with Ca(2+)-depletion period and was higher in SHR than in WKY. The rate of relaxation after washout of Phe was slower in SHR aorta compared to WKY aorta. These results, together with our earlier findings, collectively suggest that the previous known deficiency in Ca2+ pumping mechanisms of vascular muscle microsomes leading to a reduced functional size of intracellular Ca2+ pool may account for the smaller contractile response of SHR aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium and the slower rate of relaxation.

Animals↗

PubMed1991

Alpha-adrenoceptors in vascular smooth muscle: all is not well.

Studies of binding interactions and contractile responses of vascular muscles at alpha 1- and alpha 2-adrenoceptors revealed the following. (1) Agonists at alpha 1- and alpha 2-adrenoceptors may achieve selectivity by virtue of different efficacies despite similar affinities at the two receptors as well as by differing affinities. This implies that their potencies in binding studies may not correlate with potencies in response and that an agonist may produce positive or negative interactions by occupying both alpha 1- and alpha 2-receptors. (2) Agonists at alpha 2-adrenoceptors have the ability in some vascular muscles to release internal Ca2+ (implying an inositol triphosphate mechanism) as well as open Ca2+ channels. However, their contractile abilities are not closely related to function of Na+/H+ or Na+/Ca2+ exchange sites. Amiloride derivatives probably inhibit contractile effects of alpha-agonists and K+ elevation by an action at sites distal to the receptor or Ca channels. (3) The failure of alpha 2-agonists to contract arteries in vitro is not related to the absence of these receptors but most likely to their uncoupling from contractile responses, possibly owing to changes related to the in vitro condition (loss of modulating endogenous substances present in vivo such as angiotensin II or endothelins or to changed physical conditions such as may alter function of stretch-activated channels).

Amiloride↗

PubMed1990

Evidence against the role of alpha 1-adrenoceptor reserve in buffering the inhibitory effect of nifedipine on the contractility of canine vascular smooth muscle.

The relationship between the postsynaptic alpha 1-adrenoceptor reserve and the sensitivity of vasoconstriction induced by alpha-adrenoceptor agonists to the dihydropyridine Ca2+ entry blocker nifedipine was investigated in isolated muscle strips of dog mesenteric artery (DMA) and saphenous vein (DSV). The amplitudes of the contractile responses of DMA induced by phenylephrine were the same as those in DSV in the presence and in the absence of extracellular Ca2+. The use of 3 x 10(-9) M phenoxybenzamine to irreversibly block the alpha 1-adrenoceptors revealed a marked difference in the size of the alpha 1-adrenoceptor reserve between DMA (40%) and DSV (7%). In spite of a larger receptor reserve, the contractile responses induced by phenylephrine in DMA were more sensitive to nifedipine compared with those in DSV. These results suggest that the postsynaptic alpha 1-adrenoceptor reserve in vascular smooth muscle, at least in DMA and DSV, does not play an important role in buffering the inhibitory effect of nifedipine on the contractile response to a full agonist of alpha 1-adrenoceptors. Other factors, such as the difference in the membrane depolarizing effect, the ability to utilize intracellular Ca2+ for contraction, and the possible existence of alpha 1-adrenoceptor subtypes, may contribute to the different inhibitory effects of nifedipine on these blood vessels.

Animals↗