Biomedical subjects

H I Chen

Publications and source records attributed to H I Chen.

At least 37 records · Page 2Linked to original sources

PubMed1999

Effects of nitric oxide synthase inhibitors on systemic hypotension, cytokines and inducible nitric oxide synthase expression and lung injury following endotoxin administration in rats.

Endotoxin shock is characterized by systemic hypotension, hyporeactiveness to vasoconstrictors and acute lung edema. A nitric oxide synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA) has been shown to be effective in reversing acute lung injury. In the present study, we evaluated the effects of NOS blockade by different mechanisms on the endotoxin-induced changes. In anesthetized rats, lipopolysaccharide (LPS, Klebsiella pneumoniae) was administered intravenously in a dose of 10 mg/kg. LPS caused sustained systemic hypotension accompanied by an eightfold increase of exhaled NO during an observation period of 4 h. After the experiment, the lung weight was obtained and lung tissues were taken for the determination of mRNA expressions of inducible NOS (iNOS), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha-(TNF-alpha). Histological examination of the lungs was also performed. In the control group injected with saline solution, mRNA expressions of iNOS, IL-1beta and TNF-alpha were absent. Four hours after LPS, the mRNA expressions of iNOS and IL-1beta were still significantly enhanced, but TNF-alpha was not discernibly expressed. LPS also caused a twofold increase in lung weight. Pathological examination revealed endothelial damage and interstitial edema. Various NOS inhibitors were given 1 h after LPS administration. These agents included Nomega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), a constitutive NOS and iNOS inhibitor; S, S'-1,4-phenylene-bis-(1,2-ethanedinyl) bis-isothiourea dihydrobromide (1,4-PBIT, 10 mg/kg), a relatively specific iNOS inhibitor, and dexamethasone (3 mg/kg), an inhibitor of iNOS expression. These NOS inhibitors all effectively reversed the systemic hypotension, reduced the exhaled NO concentration and prevented acute lung injury. The LPS-induced mRNA expressions of iNOS and IL-1beta were also significantly depressed by these NOS inhibitors. Our results suggest that NO production through the iNOS pathway is responsible for endotoxin-induced lung injury. Certain cytokines such as IL-1beta are possibly involved. These changes are minimized by NOS inhibitors through different mechanisms.

Animals↗

PubMed1999

Effects of intracranial hypertension on steady and pulsatile haemodynamics in dogs.

1. Intracranial hypertension (ICH) tends to elicit various cardiovascular changes. Previous studies on the haemodynamic responses to ICH have been confined mainly to measurements of arterial pressure (AP), cardiac output (CO) and total peripheral resistance (TPR). In the present study, we used the technique of arterial impedance analysis for a complete assessment of steady and pulsatile haemodynamics in ICH. 2. In anaesthetized dogs, aortic pressure and flow waves were obtained with high-fidelity Millar sensors. The pressure and flow waves were subjected to Fourier transformation (frequency analysis) for an analysis of impedance spectra. Intracranial pressure (ICP) was elevated by inflation of an epidural balloon. At an ICP of 50 mmHg, the changes in steady and pulsatile haemodynamics were slight. 3. Haemodynamic changes became evident at an ICP of 100 mmHg. The mean AP was elevated by 31 mmHg (+32%) and heart rate (HR) was reduced by 25 b.p.m. (-18%). There was also a significant decrease in CO by 27% and large increase in TPR by 82%. With respect to pulsatile haemodynamics, an elevation of ICP to 100 mmHg caused significant increases in characteristic impedance by 45% and wave reflection by 53%. Arterial compliance was reduced by 50%. The ventricular oscillatory work was increased without a significant change in steady work. 4. The results indicate that ICH causes constriction of resistance vessels to affect AP and TPR. Because the pulsatile haemodynamics reflect mainly the Windkessel functions, ICH also induces stiffness of the large vessels to affect arterial impedance, pulse wave reflection and ventricular oscillatory work.

Animals↗

PubMed1999

Welsh onion (Allium fistulosum L.) extracts alter vascular responses in rat aortae.

Welsh onion, a member of the genus Allium, has been consumed for prevention of cardiovascular disorders. However, its underlying mechanisms are still unclear. We investigated whether Welsh onion extracts (green or white portion, raw or boiled) can alter vascular responses in vitro in the thoracic aortae of Sprague-Dawley rats. The possible roles of endothelium-derived factors in the Welsh onion extract-induced vascular responses were examined by applying various inhibitors, such as Nomega-nitro-L-arginine (10(-4) M), tetraethylammonium (10(-3) M), and SQ29548 (10(-5) M). Our results showed that Welsh onion extracts caused vasodilation on precontracted vessel rings. These effects were most pronounced in vessel rings treated with raw green-leaf extract (RG). Low doses of RG induced vasorelaxation, which was mediated by endothelium-derived nitric oxide. High doses of RG induced endothelium-independent vasorelaxation. On the other hand, the boiled Welsh onion extract also stimulated the release of an endothelium-derived contracting factor, which might be thromboxane A2. We conclude that Welsh onion extract can modulate vascular tone in both endothelium-dependent and endothelium-independent manners.

Allium↗

PubMed1999

Antioxidant administration inhibits exercise-induced thymocyte apoptosis in rats.

PURPOSE: The purpose of this study was to investigate the effect of antioxidant on exercise-induced apoptosis in rat thymocytes. METHODS: After exercise at 13.8 m x min(-1) for 60-90 min x d(-1) on a motor-driven drum exerciser for 2 consecutive days, rat thymocyte apoptosis was monitored by the feature of DNA fragmentation. To study the effect of antioxidant, rats were administered with butylated hydroxyanisole (BHA) for 7 d before exercise. RESULTS: Exercise could induce thymocyte DNA fragmentation as detected on electrophoretic gel and by cell death detection ELISA kit. Further studies indicated that pretreatment with antioxidant BHA to rats resulted in a blockage of exercise-induced DNA fragmentation. The concentrations of glutathione (GSH) were not significantly changed in rat thymocytes after exercise with or without BHA treatment. CONCLUSION: These results suggest that reactive oxygen species may play a role in thymocyte apoptosis induced by exercise. However, changes in GSH levels were not observed in this exercise model.

Analysis of Variance↗

PubMed1999

Modulatory effect of blood cells on hypoxic vasoconstriction response and nitric oxide release in rat lungs.

In this study, we investigated the modulatory effects of different types of blood cells on hypoxic pulmonary vasoconstrictive (HPV) response and nitric oxide (NO) release in isolated rat lungs. The lungs were perfused at a constant flow with physiologic saline solution (PSS). The changes in pulmonary arterial pressure (PAP) and NO release were observed. Two hypoxic challenges with a 5% CO2-95% N2 gas mixture were carried out in each experiment. Hypoxia induced pulmonary vasoconstriction, as reflected by an increase in PAP (0.88 +/- 0.22 cmH2O). At the same time, NO (342.9 +/- 78.3 mv) release from the lungs was also increased. Addition of white blood cells (WBCs, 0.70 to 0.88 x 10(5)/mL), platelets (1.48 to 1.96 x 10(5)/mL), or red blood cells (RBCs, 4.6 to 6.6 x 10(5)/mL) into the perfusate produced different effects on PAP and NO changes. WBCs decreased the pulmonary vasoconstriction response and this was accompanied by an increase in NO release. Platelets had no significant effects on either PAP or NO. RBCs significantly potentiated the PAP increase and attenuated the NO release. The results indicate that NO release during hypoxia tends to offset pulmonary vasoconstriction and that NO release and HPV response are modulated by different cell elements.

Animals↗

PubMed1999

Hemodynamic and neurohumoral changes after abdominal aortic constriction in rats.

Cardiac after-load, neurohumoral reaction and the secondary cardiac hypertrophy were studied in six groups of Sprague-Dawley (SD) rats with abdominal aortic constriction. We found that abdominal aortic constriction above the renal arteries decreased the heart rate and cardiac output, and increased the pulse pressure. These abnormalities would return to normal after constriction ended. Captopril, propranolol and prazosin could reduce the increase of pulse pressure but still had decreased in cardiac output of rats with abdominal constriction. Aortic constriction also increased the aortic impedance and cardiac load but decreased aortic compliance. These changes could also be lessened by captopril, propranolol and prazosin. We have confirmed that aortic constriction can induce secondary cardiac hypertrophy, but the pathogenesis might be due to multiple factors.

Animals↗

PubMed1999

[Neural and hemodynamic mechanisms of neurogenic pulmonary edema].

Acute pulmonary edema has been reported in man and animals with intracranial disorders, head trauma or cerebral compression. In anesthetized rats, cerebral compression produced acute, fulminating and fatal lung injury. Intense activation of the sympathetic mechanism in the brain stem induced systemic hypertension and a series of hemodynamic changes. Pulmonary volume loading was the result of drastic decrease in aortic flow accompanying a decline in pulmonary arterial flow. The acute increase in pulmonary blood volume caused severe rises in pulmonary arterial and venous pressures leading to disruption of lung vessels.

Animals↗

PubMed1998

Effects of chronic exercise on muscarinic receptor-mediated vasodilation in rats.

Previous studies have demonstrated that vascular responses to acetylcholine (ACh), an endothelium-dependent vasodilator, are enhanced in exercise-trained animals. In order to see if chronic exercise upregulates endothelial muscarinic (M) receptor, the subtype of M receptors responsible for ACh-induced vasorelaxation in the thoracic aorta of male Wistar rats was characterized first, then a receptor assay was performed. These animals were divided into exercise and control groups. The trained rats ran on a treadmill with a moderate intensity for 60 min per day, 5 days per week. After 10 weeks of training, rats were decapitated and their thoracic aortae were isolated. The subclass of M receptor in endothelium was pharmacologically identified on the basis of selective affinity of antagonists; ie, pirenzepine for M1, gallamine for M2, and 4-diphenylacetoxy-N-methylpiperidine methiodide for M3. Our results showed that in the thoracic aorta of Wistar rats, 1) ACh-induced vasorelaxation was mediated by M3 receptor; 2) chronic exercise enhanced ACh-evoked vasodilating responses. However, this alteration was not caused by receptor upregulation, as maximal binding sites and affinity of M3 receptor were not changed by chronic exercise. Other possible mechanisms need to be further studied.

Acetylcholine↗

PubMed1998

Development and evaluation on transdermal delivery of enoxacin via chemical enhancers and physical iontophoresis.

Iontophoresis and enhancers were performed to enhance percutaneous absorption of enoxacin so as to compare the enhancement between these two enhancing methods. The cationic surfactant of benzalkonium chloride showed the highest enhancing activity for enoxacin for all pH values of buffer vehicles. The enhancement factor of sodium laurylsulfate showed a dose-dependent property between the range of 0.1% to 3.0% concentration. Nonionic surfactant of Polysorbate 80 did not exhibit any enhancing effect on the percutaneous absorption of enoxacin. The highest enhancement factor of iontophoretic delivery was observed at pH 5.0 solution of anodal iontophoresis for cationic enoxacin. The cathodal iontophoresis of negative molecules and anodal iontophoresis of neutral molecules showed lower enhancing effect for enoxacin. The fact that the skin residuals of enoxacin after iontophoresis showed both tremendous and current density-dependent amounts for cationic enoxacin suggested local skin and soft tissue infections might be treated by this physical enhancement method. Combination of benzalkonium chloride and iontophoresis exerted a synergistic effect for anionic enoxacin in pH 10.0, which was possibly due to the shielding of negative charge in skin and the water molecules carried by chloride.

Administration, Cutaneous↗

PubMed1997

Role of prostaglandins in regulation of cerebral blood flow during acute hypertension.

Endothelium-derived prostaglandins appear to play an important role in myogenic contraction of the cerebral arteries in response to increased transmural pressure. The goal of this study was to determine whether prostaglandins contribute to the autoregulatory response of cerebral blood flow (CBF) during acute hypertension in normotensive and chronically hypertensive animals. In 4-5 months old Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) anesthetized with pentobarbital sodium (45 mg/kg, i.p.), regional CBF of the right parietal cortex was monitored by laser-Doppler flowmetry. Acute hypertension was induced by intravenous infusion of phenylephrine and the elevated arterial pressure was maintained for 50 seconds for the measurement of CBF. In the control group of WKY rats, CBF increased by 5.6% per 10-mmHg increase in arterial pressure. Changes in CBF were similar between the initial state (0-10 seconds) and the steady state (30-40 seconds) of acute hypertension. In WKY rats pretreated with indomethacin (10 mg/kg, i.v.), increases in CBF in the initial state were slightly but significantly greater than that in the steady state. Indomethacin also tended to enhance the increases in CBF in both the initial state and the steady state; however, the effect was not significant. In the control group and indomethacin-pretreated group of SHR, acute hypertension produced similar increases in CBF. In both groups, no significant difference between changes in CBF in the initial state and the steady state was observed. Thus our findings suggest that 1) in normotensive animals, the early autoregulatory response of CBF during acute hypertension is partially mediated by prostaglandins and 2) the role of prostaglandins in the regulation of CBF during acute hypertension is altered in chronically hypertensive animals.

Acute Disease↗

PubMed1997

Characterization of the WW domain of human yes-associated protein and its polyproline-containing ligands.

We had previously identified the WW domain as a novel globular domain that is composed of 38-40 semiconserved amino acids and is involved in mediating protein-protein interaction. The WW domain is shared by proteins of diverse functions including structural, regulatory, and signaling proteins in yeast, nematode, and mammals. Functionally it is similar to the Src homology 3 domain in that it binds polyproline ligands. By screening a 16-day mouse embryo expression library, we identified two putative ligands of the WW domain of Yes kinase-associated protein which we named WW domain-binding proteins 1 and 2. These proteins interacted with the WW domain via a short proline-rich motif with the consensus sequence of four consecutive prolines followed by a tyrosine. Herein, we report the cDNA cloning and characterization of the human orthologs of WW domain-binding proteins 1 and 2. The products encoded by these cDNA clones represent novel proteins with no known function. Furthermore, these proteins show no homology to each other except for a proline-rich motif. By fluorescence in situ hybridization on human metaphase chromosomes, we mapped the human genes for WW domain-binding proteins 1 and 2 to chromosomes 2p12 and 17q25, respectively. In addition, using site-directed mutagenesis, we determined which residues in the WW domain of Yes kinase-associated protein are critical for binding. Finally, by synthesizing peptides in which the various positions of the four consecutive proline-tyrosine motif and the five surrounding residues were replaced by all possible amino acid residues, we further elucidated the binding requirements of this motif.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Prevalence of diabetes mellitus and impaired glucose tolerance in Aborigines and Chinese in eastern Taiwan.

The aim of this study was to determine the prevalence of diabetes mellitus and impaired glucose tolerance (IGT) in three different ethnic groups in eastern Taiwan. The study was performed among Han Chinese, aboriginal Ami and aboriginal Atayal in six rural villages. Inhabitants aged 40 years and over were invited to participate. A 75-g oral glucose tolerance test (OGTT) was used as suggested by the World Health Organization (WHO) for population screening purposes. WHO criteria were used for determining the results. A total of 1013 adults (460 men and 553 women) were examined with a response rate of 62.1%. There were no significant differences in sex, age and history of diabetes between responders and non-responders. The age-adjusted prevalence of diabetes was 11.0% (9.8% in men and 12.3% in women) in the Chinese, 9.1% (12.1% in men and 7.4% in women) in the Amis, 10.8% (11.5% in men and 9.4% in women) in the Atayal and 9.9% (11.5% in men and 8.5% in women) for the two aboriginal groups together. Although sex differences in prevalence of diabetes were not statistically significant, it seems that diabetes was slightly more prevalent in Chinese women than in Chinese men (12.3 versus 9.8%). Nonetheless, the prevalence rate of diabetes was somewhat higher in the aboriginal males than in the aboriginal females (12.1 versus 9.8% for Ami and 11.5 versus 10.7% for Atayal). The prevalence of IGT was 7.2, 8.5, 10.8 and 9.7% for the Chinese, Amis, Atayal and the two aboriginal groups, respectively. There were no substantial differences in the prevalence of diabetes and IGT among these three ethnic groups. Environment, rather than ethnicity, was more likely the predominant factor. It was found that the prevalence of diabetes in this study was about twice as high as that reported in a 1987 survey in Taiwan. The discrepancy may be due to different screening methods and assessment periods.

Adult↗

PubMed1997

Acute effects of nitric oxide blockade with L-NAME on arterial haemodynamics in the rat.

1. We employed the technique of impedance spectral analysis to investigate the role of endogenous nitric oxide (NO) in the regulation of steady and pulsatile haemodynamics in Wistar Kyoto rat (WKY). 2. A total of 12 WKYs was anaesthetized with pentobarbitol sodium (40 mg kg-1, i.p.) and artificially ventilated with an animal respirator. The aortic pressure wave was monitored with a high fidelity Millar sensor, and aortic flow wave with an electromagnetic flow probe. The pressure and flow waves were subjected to Fourier transform for the analysis of impedance spectra. 3. The baseline cardiovascular parameters were mean arterial pressure (APm) 95 +/- 9 mmHg, heart rate (HR) 338 +/- 9 b.p.m., stroke volume (SV) 0.23 +/- 0.01 ml, cardiac output (CO) 77.8 +/- 1.6 ml min-1, total peripheral resistance (TPR) 98 +/- 11 (x10(3)) dyne s cm-5, characteristic impedance (Zc) 2046 +/- 141 dyne s cm-5, arterial compliance at mean AP (Cm) 3.78 +/- 0.22 microliters mmHg-1 and backward pulse wave (Pb) 12.9 +/- 0.6 mmHg. 4. An NO synthase inhibitor, NG-nitro-L-arginine monomethyl ester (L-NAME) was administered at graded intravenous doses. This agent caused dose-dependent increases in AP and TPR with decreases in HR. At an accumulative dose of 10 mg kg-1, APm was increased by 29 +/- 3 mmHg (+31%) and TPR by 49 +/- 6 (x10(3)) dyne s cm-5 (+50%), while HR was reduced by 37 +/- 5 b.p.m. (-11%) and CO by 10.4 +/- 0.8 ml min-1 (-14%). The pulsatile haemodynamics including Zc and Pb were slightly increased by 14-15%. Cm was decreased by 1.09 microliters mmHg-1 (-29%). L-NAME also did not significantly affect the ventricular work including the steady, oscillatory and total work. 5. Aminoguanidine, a specific inhibitor for inducible NO synthase (iNOS), in dose 10-60 mg kg-1 i.v. did not alter the AP, HR and other parameters. The result indicated that blockade of constitutive NOS, but not iNOS is involved in these changes. 6. Angiotensin II (Ang) in various infusion doses was used to produce a profile of AP increase similar to that caused by L-NAME. Ang remarkably increased Zc, while TPR was moderately elevated. The pattern of haemodynamic changes was different from that following L-NAME. 7. The results suggest that blockade of the endogenous NO affects predominantly the arterial pressure and peripheral resistance. The Windkessel functions such as arterial impedance and pulse wave reflection are slightly increased. Ventricular works are not significantly altered.

Animals↗

PubMed1997

Endogenous nitric oxide on arterial hemodynamics: a comparison between normotensive and hypertensive rats.

Endogenous nitric oxide (NO) plays an important role in maintaining a vasodilator tone. In the present study, we compared the effects of NO blockade on the steady and pulsatile components of arterial hemodynamics between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto strain (WKY), 22-26 wk of age. In the first series of experiments, various doses (1-30 mg/kg i.v.) of N(G)-nitro-L-arginine methyl ester (L-NAME) were administered to block the NO release in anesthetized WKY and SHR. In both WKY and SHR, L-NAME caused a dose-dependent increase in arterial pressure (AP) with a decrease in heart rate (HR). The maximal effects of L-NAME on AP and HR occurred at a dose of 10 mg/kg. Both the AP increase and HR decrease were higher in SHR (AP, +38 +/- 4 mmHg; HR, -49 +/- 5 beats/min) than WKY (AP, +22 +/- 3 mmHg; HR, -33 +/- 5 beat/min). In other series, the technique of impedance spectral analysis was employed to investigate the effects of L-NAME (10 mg/kg i.v.) on the arterial hemodynamics. The aortic pressure and flow waves were recorded and subjected to Fourier transform for the analysis of impedance spectra. Both in WKY (n = 12) and in SHR (n = 12), L-NAME significantly increased AP and total peripheral resistance (TPR). The pulsatile and frequency-dependent hemodynamics including characteristic impedance, wave reflection, and ventricular work were only slightly altered. Despite higher resting values of AP and TPR in SHR (mean AP, 154 +/- 7 mmHg; mean TPR, 204 +/- 17 x 10(3) dyn x s x cm(-5)) than WKY (mean AP, 94 +/- 6 mmHg; mean TPR, 98 +/- 12 x 10(3) dyn x s x cm(-5)), the magnitudes of AP and TPR increments after NO blockade were significantly higher in SHR (AP, +37 +/- 3 mmHg; TPR, +124 +/- 16 x 10(3) dyn x s x cm(-5)) than in WKY (AP, +24 +/- 3 mmHg; TPR, +45 +/- 7 x 10(3) dyn x s x cm(-5)). The continuous formation of endogenous NO affects predominantly the AP and peripheral resistance in both WKY and SHR. The windkessel functions, such as impedance spectra, pulse-wave reflection, and ventricular work, are less affected after NO blockade. In addition, the effects of NO release on the AP and TPR appear to be enhanced in rats with established hypertension.

Animals↗

PubMed1997

Effects of chronic exercise and deconditioning on platelet function in women.

To investigate the effects of chronic exercise and deconditioning on platelet function in women, 16 healthy sedentary women were divided into control and exercise groups. The exercise group cycled on an ergometer at 50% maximal oxygen consumption for 30 min/day, 5 days/wk, for two consecutive menstrual cycles and then were deconditioned for three menstrual cycles. During this period, platelet adhesiveness on a fibrinogen-coated surface, ADP-induced platelet aggregation and intracellular calcium concentration elevation, guanosine 3',5'-cyclic monophosphate (cGMP) content in platelets, and plasma nitric oxide metabolite levels were measured before and immediately after a progressive exercise test in the midfollicular phase. Our results indicated that, after exercise training, 1) resting heart rates and blood pressures were reduced, and exercise performance was improved; 2) resting platelet function was decreased, whereas plasma nitrite and nitrate levels and platelet cGMP contents were enhanced; and 3) the potentiation of platelet function by acute strenuous exercise was decreased, whereas the increases in plasma nitrite and nitrate levels and platelet cGMP contents were enhanced by acute exercise. Furthermore, deconditioning reversed these training effects. This implies that training-induced platelet functional changes in women in the midfollicular phase may be mediated by nitric oxide.

Adult↗

PubMed1997

Effects of short-term exercise on female platelet function during different phases of the menstrual cycle.

Previous studies have shown that premenopausal women have a low incidence of cardiovascular diseases, and that acute exercise affects male platelet function in an intensity-dependent manner. To investigate whether acute exercise affects female platelet function differently from males, sixteen sedentary women in the midfollicular phase or midluteal phase received strenuous or moderate exercise on a bicycle ergometer. Before and immediately after exercise, platelet adhesiveness, adenosine diphosphate-induced platelet aggregation and intracellular calcium concentration elevation, platelet cAMP and cGMP contents, urinary 11-dehydro-TXB2 and 6-keto-prostaglandin F1 alpha levels, and plasma nitric oxide metabolite level were determined. Our results showed no differences in exercise performance and in resting platelet function between two menstrual phases, with little change in urinary eicosanoid metabolites and platelet cAMP levels under all experimental conditions. In addition, for women in the midfollicular phase, (1) strenuous exercise increased platelet adhesiveness, adenosine-diphosphate-induced platelet aggregation, and intracellular calcium concentration elevation, whereas moderate exercise suppressed them; (2) moderate exercise enhanced plasma nitric oxide metabolite and platelet cGMP levels. In contrast, none of these platelet functions was affected by acute exercise in the midluteal phase. Therefore, we conclude that acute exercise affects female platelet function in an intensity-dependent manner in the midfollicular phase but not in the midluteal phase. The irresponsiveness of platelets to acute exercise in the luteal phase may partially explain why premenopausal women have a lower incidence of cardiovascular diseases than men.

Adult↗

PubMed1996

Changes in cytosolic calcium concentrations and cell morphology in single platelets adhered to fibrinogen-coated surface under flow.

Changes in intracellular calcium concentration [Ca2+]i of fura-2-loaded human platelet during its adhesion to a fibrinogen-coated surface were studied, using a flow chamber mounted on an epifluorescence microscope equipped with digital-ratio imaging. Adherent platelets were individually mapped under a scanning electron microscope to establish the possible correlation between adhesion-associated shape alterations and [Ca2+]i changes. We found that 1) there was no immediate [Ca2+]i elevation on platelet adhesion; 2) [Ca2+]i changes varied drastically platelets with a lag time ranging 10 to 200 s, averaging about 1 minute; 3) the pattern of [Ca2+]i changes varied drastically among individual adherent platelets; 4) the degree of [Ca2+]i elevation appeared to correlate with the extent of morphology change, with the vast majority ( > 90%) of spread platelets showed detectable [Ca2+]i changes; 5) neither morphological nor [Ca2+]i changes correlated with the lag time; 6) platelets treated with dimethyl-BAPTA (15 mumol/L) underwent normal shape change without [Ca2+]i elevation; 7) cytochalasin D (10 mumol/L) inhibited both shape change and [Ca2+]i elevation; 8) colchicine (1 mmol/L) was ineffective in both regards. We conclude that although platelet adhesion-associated shape changes may be accompanied with heterogeneous [Ca2+]i changes that are microfilament-dependent, [Ca2+]i changes do not happen immediately after platelet-surface contact and they are not required for adherent platelets to undergo postcontact morphological changes.

Blood Platelets↗

PubMed1996

Pulmonary edema induced by phorbol myristate acetate is attenuated by compounds that increase intracellular cAMP.

We have investigated the effect of terbutaline, aminophylline and dibutyryl cyclic AMP (DBcAMP) on phorbol myristate acetate (PMA)-induced acute lung injury in isolated, blood-perfused rabbit lungs. Pulmonary arterial pressure and lung weight were measured for 30 min after a bolus injection of PMA (10 mu g/kg). In the group exposed to PMA alone, the mean pulmonary arterial pressure (PAP) increased from 16.33 + or - 1.28 to 77.30 + or - 6.40 mmHg (P <0.001), and lung weight increased by 70.69 + or - 10.94 g during the 30 min after PMA challenge (P<0.001). Pretreatment with terbutaline, aminophylline or DBcAMP prevented the increases in both PAP and lung weight (P <0.001). Each of the three drugs also prevented the increase in pulmonary vascular permeability induced by PMA: terbutaline, aminophylline, and DBcAMP all significantly reduced the pulmonary capillary filtration coefficient (KfC) as well as the albumin concentration in the lung lavage fluid after PMA exposure. Post-treatment with terbutaline 5 min after PMA administration also had a protective effect. The mechanisms responsible for these protectivp3 effects may all involve an increase in intracellular cAMP, since all three drugs increase cAMP in the lung (though by different mechanisms). Our data further indicate that the inhibition of tumor necrosis factor production may likewise play an important role in the protective effect exerted by these drugs.

Adrenergic beta-Agonists↗