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Li-Fan Zhang

Publications and source records attributed to Li-Fan Zhang.

15 recordsLinked to original sources
PubMed2005

[Enhanced BK(Ca) single-channel activities in cerebrovascular smooth muscle cells of simulated microgravity rats.].

The aim of the present study was to investigate the changes in single-channel currents of large conductance calcium-activated potassium channels (BK(Ca) channels) in cerebral vascular smooth muscle cells (VSMCs) of rats after 1-week simulated microgravity. Sprague-Dawley rats were subjected to tail-suspension (SUS) to simulate cardiovascular deconditioning due to microgravity. Cytosolic calcium ([Ca(2+)](i)) was examined by laser-scanning confocal microscopy with calcium-sensitive-dye Fluo-3/AM as fluorescent probe. Single-channel currents of BK(Ca) channels were measured with cell-attached membrane patches bathed in symmetrical high potassium solution. The [Ca(2+)](i)i level was significantly higher in cerebrovascular myocytes of SUS than that of control (CON) rats. The probability of open (Po) and the mean open time (To) of BK(Ca) channels in cerebral VSMCs significantly increased in SUS as compared with CON. However, there were no significant differences in the unitary conductance and mean close time (Tc) between the two groups. The results obtained suggest that both the elevated [Ca(2+)](i) and enhanced single-channel activities of BK(Ca) channels in cerebral VSMCs might be among the electrophysiological mechanisms that mediate the increased vasoreactivity and hypertrophic change in cerebral arteries during adaptation to simulated microgravity in rats.

English Abstract↗
PubMed2005

Functional alterations in cerebrovascular K(+) and Ca(2+) channels are comparable between simulated microgravity rat and SHR.

Exposure to microgravity leads to a sustained elevation in transmural pressure across the cerebral vasculature due to removal of hydrostatic pressure gradients. We hypothesized that ion channel remodeling in cerebral vascular smooth muscle cells (VSMCs) similar to that associated with hypertension may occur and play a role in upward autoregulation of cerebral vessels during microgravity. Sprague-Dawley rats were subjected to 4-wk tail suspension (Sus) to simulate the cardiovascular effect of microgravity. Large-conductance Ca(2+)-activated K(+) (BK(Ca)), voltage-gated K(+) (K(V)), and L-type voltage-dependent Ca(2+) (Ca(L)) currents of Sus and control (Con) rat cerebral VSMCs were investigated with a whole cell voltage-clamp technique. Under the same experimental conditions, K(V), BK(Ca), and Ca(L) currents of cerebral VSMCs from adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were also investigated. K(V) current density decreased in Sus rats vs. Con rats [1.07 +/- 0.14 (n = 22) vs. 1.31 +/- 0.28 (n = 16) pA/pF at +20 mV (P < 0.05)] and BK(Ca) and Ca(L) current densities increased [BK(Ca): 1.70 +/- 0.37 (n = 23) vs. 0.88 +/- 0.22 (n = 19) pA/pF at +20 mV (P < 0.05); Ca(L): -2.17 +/- 0.21 (n = 35) vs. -1.31 +/- 0.10 (n = 26) pA/pF at +10 mV (P < 0.05)]. Similar changes were also observed in SHR vs. WKY cerebral VSMCs: K(V) current density decreased [1.03 +/- 0.33 (n = 9) vs. 1.62 +/- 0.64 (n = 9) pA/pF at +20 mV (P < 0.05)] and BK(Ca) and Ca(L) current densities increased [BK(Ca): 2.54 +/- 0.47 (n = 11) vs. 1.12 +/- 0.33 (n = 12) pA/pF at +20 mV (P < 0.05); Ca(L): -3.99 +/- 0.53 (n = 12) vs. -2.28 +/- 0.20 (n = 10) pA/pF at +20 mV (P < 0.05)]. These findings support our hypothesis, and their impact on space cardiovascular research is discussed.

Animals↗
PubMed2005

[Changes in voltage-dependent calcium channel currents of vascular smooth muscle cells isolated from small mesenteric arteries of simulated weightless rats].

The aim of the present study was to examine the changes in the function of voltage-dependent calcium channels (VDC) of vascular smooth muscle cells (VSMCs) isolated from small mesenteric arteries of rats subjected to 1-week or 4-week simulated weightlessness. The whole-cell recording mode was used to record current densities and Ba(2+) was used as charge carrier. Curves and fitting parameters describing steady-state activation and inactivation characteristics of VDC were thus obtained. The inward currents recorded from the VSMCs of small mesenteric arteries were mainly the Ba(2+) currents through the long-lasting type VDC (L-VDC). Compared with that of the control rats, the L-VDC current density of VSMCs from small mesenteric arteries showed a trend toward a decrease in the rats after 1-week , while a significant decrease was observed in the rats after 4-week simulated weightlessness. However, there were no significant differences in the opening and closing rates of L-VDCs, the position of steady-state activation and inactivation curves, and in the parameters, V(0.5) and k, between either of the two groups and its respective control group. The membrane capacitance and the reversal potential of the VSMCs from the small mesenteric arteries of rats after simulated weightlessness also showed no significant changes. These findings suggest that the decreased function of the L-VDC in hindquarter VSMCs might be one of the electrophysiological mechanisms that mediate the depressed vasoreactivity and atrophic change in hindquarter arteries during adaptation to simulated weightlessness in rats.

Animals↗
PubMed2004

Differential activation of potassium channels in cerebral and hindquarter arteries of rats during simulated microgravity.

The purpose of this study was to test the hypothesis that differential autoregulation of cerebral and hindquarter arteries during simulated microgravity is mediated or modulated by differential activation of K(+) channels in vascular smooth muscle cells (VSMCs) of arteries in different anatomic regions. Sprague-Dawley rats were subjected to 1- and 4-wk tail suspension to simulate the cardiovascular deconditioning effect due to short- and medium-term microgravity. K(+) channel function of VSMCs was studied by pharmacological methods and patch-clamp techniques. Large-conductance Ca(2+)-activated K(+) (BK(Ca)) and voltage-gated K(+) (K(v)) currents were determined by subtracting the current recorded after applications of 1 mM tetraethylammonium (TEA) and 1 mM TEA + 3 mM 4-aminopyridine (4-AP), respectively, from that of before. For cerebral vessels, the normalized contractility of basilar arterial rings to TEA, a BK(Ca) blocker, and 4-AP, a K(v) blocker, was significantly decreased after 1- and 4-wk simulated microgravity, respectively. VSMCs isolated from the middle cerebral artery branches of suspended rats had a more depolarized membrane potential (E(m)) and a smaller K(+) current density compared with those of control rats. Furthermore, the reduced total current density was due to smaller BK(Ca) and smaller K(v) current density in cerebral VSMCs after 1- and 4-wk tail suspension, respectively. For hindquarter vessels, VSMCs isolated from second- to sixth-order small mesenteric arteries of both 1- and 4-wk suspended rats had a more negative E(m) and larger K(+) current densities for total, BK(Ca), and K(v) currents. These results indicate that differential activation of K(+) channels occur in cerebral and hindquarter VSMCs during short- and medium-term simulated microgravity. It is further suggested that different profiles of channel remodeling might occur in VSMCs as one of the important underlying cellular mechanisms to mediate and modulate differential vascular adaptation during microgravity.

Animals↗
PubMed2004

Daily short-period gravitation can prevent functional and structural changes in arteries of simulated microgravity rats.

This study was designed to clarify whether simulated microgravity-induced differential adaptational changes in cerebral and hindlimb arteries could be prevented by daily short-period restoration of the normal distribution of transmural pressure across arterial vasculature by either dorsoventral or footward gravitational loading. Tail suspension (Sus) for 28 days was used to simulate cardiovascular deconditioning due to microgravity. Daily standing (STD) for 1, 2, or 4 h, or +45 degrees head-up tilt (HUT) for 2 or 4 h was used to provide short-period dorsoventral or footward gravitational loading as countermeasure. Functional studies showed that Sus alone induced an enhancement and depression in vasoconstrictor responsiveness of basilar and femoral arterial rings, respectively, as previously reported. These differential functional alterations can be prevented by either of the two kinds of daily gravitational loading treatments. Surprisingly, daily STD for as short as 1 h was sufficient to prevent the differential functional changes that might occur due to Sus alone. In morphological studies, the effectiveness of daily 4-h HUT or 1-h STD in preventing the differential remodeling changes in the structure of basilar and anterior tibial arteries induced by Sus alone was examined by histomorphometry. The results showed that both the hypertrophic and atrophic changes that might occur, respectively, in cerebral and hindlimb arteries due to Sus alone were prevented not only by daily HUT for 4 h but also by daily STD even for 1 h. These data indicate that daily gravitational loading by STD for as short as 1 h is sufficient to prevent differential adaptational changes in function and structure of vessels in different anatomic regions induced by a medium-term simulated microgravity.

Adaptation, Physiological↗
PubMed2004

Model of depressed myocardium shows orthostatic intolerance with or without reduced blood volume.

INTRODUCTION: The development of orthostatic hypotension (OH) is complex and multi-factorial. Previous simulation work indicates that myocardial contractility depression (MCD) may increase OH when there is a total blood volume decrease. This paper hypothesized that MCD increased OH in both humans with and without decrease in blood volume. METHODS: A model, which was previously used to reproduce cardiovascular response to lower body negative pressure (LBNP), hypovolemia, and MCD, was modified by incorporating the physiologic mechanism of plasma filtration into the interstitium during LBNP. The model was evaluated by human experimental results. Using the model, HR and BP response to LBNP were simulated at conditions of 10%, 20%, and 30% MCD. Additionally, HR and BP response to LBNP were simulated at conditions of 10% and 20% MCD with a 12% decrease in blood volume. RESULTS: Simulation results indicate that the increments of HR and decrements of systolic BP (SBP) and mean arterial pressure (MAP) rise with the increases of MCD. Specifically, simulation results indicate that about 30% MCD would cause OH (HR: 117 bpm; SBP: 92 mmHg; MAP: 78 mmHg). It also indicates that about 20% MCD would cause OH (HR: 134 bpm, SBP: 84 mmHg, MAP: 73 mmHg) with a 12% decrease in total blood volume. CONCLUSION: It is suggested that MCD increases OH whether or not there is a total blood decrease, and further suggested that MCD induced by both spaceflight and heart disease may increase OH.

Adult↗
PubMed2003

[Preparation and identification of polyclonal antiserum against angiotensinogen].

For studying the expression and distribution of angiotensinogen (AGT), the C-teminus of rat AGT gene was expressed in E.coli. Rabbits were immunized with expressed AGT protein and sera from different rabbits were raised. ELISA showed a high titre (1:25600) of the antiserum. With the antiserum, Western blotting recognized not only the prokaryotic expressed AGT, but also the endogenous AGT protein in liver tissue of both rats and humans. Using this antiserum, immunohistochemistry showed the expression of AGT protein in islet cells of human pancreas as well as in epithelium of human bile duct. These results suggest that the prokaryotic expressed AGT protein is an effective immunogen for the preparation of anti-AGT antiserum. Our present work provides an important tool for study of the pathophysiological role of AGT as well as local renin-angiotensin system.

Angiotensinogen↗
PubMed2003

Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity.

This study was designed to compare the effectiveness of daily short-duration -Gx gravity exposure in preventing adverse changes in skeletal and cardiac muscles and bone due to simulated microgravity. Tail suspension for 28 days was used to simulate microgravity-induced deconditioning effects. Daily standing (STD) at 1 G for 1, 2, or 4 h/day or centrifugation (CEN) at 1.5 or 2.6 G for 1 h/day was used to provide -Gx gravitation as a countermeasure. The results indicate that the minimum gravity exposure requirements vary greatly in different systems. Cardiac muscle is most responsive to such treatment: 1 h/day of -Gx gravitation by STD was sufficient to prevent adverse changes in myocardial contractility; bone is most resistant: 4 h/day of -Gx gravitation only partially alleviated the adverse changes in physical and mechanical properties of the femur. The responsiveness of skeletal muscle is moderate: 4 h/day of -Gx gravitation prevented mass reduction and histomorphometric changes in the soleus muscle during a 28-day simulation period. Increasing gravitational intensity to 2.6 G showed less benefit or no additional benefit in preventing adverse changes in muscle and bone. The present work suggests that system specificity in responsiveness to intermittent gravity exposure should be considered one of the prerequisites in proposing intermittent artificial gravity as a potential countermeasure.

Adrenal Glands↗
PubMed2003

Daily 4-h head-up tilt is effective in preventing muscle but not bone atrophy due to simulated microgravity.

To assess the potential value of intermittent artificial gravity as an efficient countermeasure, our previous studies have showed that daily 4-h standing (STD) is sufficient in counteracting muscle atrophy but not bone atrophy induced by simulated microgravity. The aim of the present study was to determine whether intermittent gravitational loading by daily 2-h or 4-h, +45 degrees head-up tilt (HUT) is more effective than STD in counteracting muscle and, particularly, bone atrophy due to simulated microgravity. Sprague-Dawley male rats weighing 290-300 g were subjected to a 28-d tail-suspension to simulate microgravity deconditioning. Daily HUT for 2, or 4 h was used to provide intermittent gravitational loading in foot-ward and tail-ward directions. The results showed that 4 h/d HUT was sufficient, and 2 h/d was less effective, in preventing adverse changes in muscle weights, fiber types, and cross-sectional areas (CSA) of muscles due to a 28-d simulated microgravity. The % protections by 4 h/d HUT in maintaining the CSAs of type I fibers in soleus, medial and lateral gastrocnemius and extensor digitorum longus muscles were 103%, 82%, 102%, and 83%, respectively. However, according to changes in physical and mechanical properties of femur, daily 4-h HUT was ineffective in attenuating the adverse changes in bone due to a 28-d simulated microgravity. Reductions in wet, dry, and ash weights and decreases in mechanical strength of femur did not show significant improvement by daily 2-h or 4-h HUT. Taken together, the findings indicate that the countermeasure effectiveness of daily 2-h or 4-h HUT for muscles is comparable with that by daily STD with the same durations. Daily 4-h HUT, as 4-h STD, is also ineffective in attenuating adverse changes in bone mass, but seems partially effective in preventing declines in mechanical properties due to simulated microgravity.

Animals↗
PubMed2002

[Changes in potassium currents of vascular smooth muscle cells isolated from hindquarter arteries of rats after 4 weeks simulated weightlessness].

The changes in potassium currents of vascular smooth muscle cells (VSMCs) isolated from saphenous arteries and the 2nd-6th order branches of the mesenteric arteries of 4-week tail-suspended rats (SUS) were examined using whole cell patch clamp technique. The resting potential (RP) of the VSMCs from SUS group was more negative compared with that of the control group (CON).The whole cell potassium current densities of VSMCs isolated from the saphenous arteries and small mesenteric arteries in SUS group were significantly larger than those of the CON group.The BK(Ca) and K(V) current densities of VSMCs from saphenous arteries and small mesenteric arteries from SUS group were also significantly larger than those from the CON group.It is speculated that the hyperpolarization of VSMCs and decreased calcium influx through voltage-dependent calcium channels might be one of the electrophysiological mechanisms involved in the depressed vasoreactivity of hindquarter arteries induced by simulated weightlessness.

Animals↗
PubMed2002

Effects of repeated brain ischemia induced by rapid lower body negative pressure on brain water and Na+,K+-ATPase activity in rats.

BACKGROUND: It has been demonstrated that during +Gz exposure cerebral blood flow is significantly reduced resulting in brain ischemia. Animal centrifuge models are commonly used to investigate the mechanisms of +Gz-induced loss of consciousness (G-LOC) and their pathophysiological effects on the brain. These dynamic models are limited because we currently are unable to obtain accurate measures of membrane ion flux or single cell electrophysiological responses from animals under centrifugation. HYPOTHESIS: The aim of the present study was to develop a non-centrifuge animal model of short-term, repeatable and complete brain ischemia using a rodent lower body negative pressure (LBNP), and to investigate the effects of repeated complete brain ischemia induced by LBNP on brain Na+,K+-ATPase activity, Na+, K+ and water contents in rats. METHODS: Eight anesthetized rats were exposed randomly to LBNP of -2.67 kPa, -4.00 kPa, and -5.33 kPa, respectively, at the rate of -0.67 kPa x s(-1). The pressure rapidly returned to control level when EEG became isoelectric (flat). The mean arterial BP (MAP), EEG and ECG were recorded. Twenty-one rats were divided randomly into control, single LBNP exposure, and three LBNP exposures groups (n = 7 in each group). Brain samples were analyzed for Na+,K+-ATPase activity, Na+, K+ and water contents 1 h after single and three 2-min LBNP exposures (-4.00 kPa at a rate of 0.67 kPa x s(-1)), respectively. RESULTS: MAP decreased rapidly during LBNP exposure. The mean time to isoelectric EEG was 41.33 +/- 11.48, 30.67 +/- 3.88 and 25.67 +/- 3.45 s during -2.67, -4.00 and -5.33 kPa LBNP, respectively. Heart rate (HR) significantly decreased when EEG became isoelectric. MAP, HR and EEG rapidly returned after releasing LBNP. The brain Na+,K-ATPase activity decreased significantly after single LBNP exposure and decreased further after three LBNP exposures. The brain K+, Na+ and water contents increased significantly after three LBNP exposures. CONCLUSIONS: A rat model of short-term, repeatable brain ischemia was developed using rapid LBNP. Three -4.00 kPa LBNP exposures (2 min each) cause a significant reduction in brain Na+,K+-ATPase activity and brain edema in rats.

Adenosine Triphosphatases↗
PubMed2002

Research in differential adaptations of vessels to microgravity.

The primary goal of this presentation is to look back to review the work on differential adaptation of vessels to microgravity in the past and to look forward to the future for research opportunities in this field. The main part is devoted to a discussion on the local renin-angiotensin system and ion channel mechanisms involved.

Journal Article↗
PubMed2002

Changes of angiotensinogen expression in arteries of tail-suspended rats.

Previous findings from our laboratory have demonstrated that simulated microgravity may result in atrophic changes with depressed vasoconstrictor responsiveness in hindquarter vessels, and hypertrophic changes with enhanced vasoconstrictor responsiveness in cerebral arteries of rats. However, the mechanisms of this differential adaptation are still not well understood. Local renin-angiotensin system (L-RAS) has been found to be actively involved in the remodeling of arteries. We hypothesized that L-RAS may function as a local regulatory mechanism in the microgravity-induced differential changes of arterial vessles. Angiotensinogen (AGT) is the only and indispensable substrate of local renin-angiotensin system (L-RAS). In the present work, the expression changes of AGT mRNA and protein level as well as its time course characteristics were examined.

Journal Article↗
PubMed2002

Changes in potassium currents of vascular smooth muscle cells from hindquarter arteries of 4-wk simulated weightlessness rats.

It has been reported by Delp et al and Ma J et al that the vasoreactivity of hindquarter vessels from simulated weightless rats decreased. Many factors may contribute to the depressed vasoreactivity. Because the potassium channels play an important role in regulating the resting potential and contribute to the action of some vasoactive substances, we speculated that the changes of potassium channels may be an electro-physiological mechanism involved in the depressed vasoreactivity of hindquarter vessels due to simulated weightlessness.

Journal Article↗