Biomedical subjects

H Matsuura

Publications and source records attributed to H Matsuura.

At least 19 recordsLinked to original sources

PubMed1999

Reverse motion of organelles with myosin molecules along bundles of the actin filaments in a Characean internodal cell.

We have visualized bundles of the actin filaments of a Characean internodal cell and investigated the sliding motion of organelles with myosin on the bundles. The investigation revealed that a power spectrum of the sliding velocity time series of the organelle has two remarkable peaks near 4 and 7.5 Hz. This suggests that myosin molecules attached to the organelle not independently but cooperatively produce the sliding force. Moreover, we have found that some organelles move in the opposite direction of their sliding motion for several hundred milliseconds along the bundles. The fluctuation analysis of that motion showed that a power spectrum profile of the reverse velocity time series almost agreed with that of the sliding velocity time series. This result suggests that the dynamics of the reverse motion is the same as that of the sliding motion.

Actin Cytoskeleton↗

PubMed1999

Regulation of the transglutaminase I gene. Identification of DNA elements involved in its transcriptional control in tracheobronchial epithelial cells.

The transglutaminase I (TGase I) gene encodes an enzyme that catalyzes the cross-linking of structural proteins involved in the formation of the cornified envelope during squamous cell differentiation. To identify DNA elements important for the transcriptional control of the TGase I gene, we analyzed the ability of a 2.9-kilobase pair (kb) upstream regulatory region to control the expression of a reporter gene in vivo and in vitro. Transgenic mice bearing the pTG(-2.9kb)CAT construct exhibited the same pattern of tissue-specific expression of CAT as reported for TGase I. Deletion analysis in transiently transfected rabbit tracheal epithelial cells indicated that two sequences from bp -490 to -470 and from -54 to -37 are involved in the activation of TGase I transcription. Point mutation analysis and mobility shift assays showed that the sequence located between -54 and -37 is a functional Sp1-like transcription element. Sp1 and Sp3, but not Sp2, are part of nuclear protein complexes from differentiated RbTE cells binding to this site. The element TGATGTCA between bp -490 and -470 is contained in a larger 22-bp palindrome and resembles the consensus cAMP response element-binding protein (CREB)/AP-1 element recognized by dimeric complexes of members of the CREB, ATF, Fos, and Jun families. Mutations in this sequence greatly reduced promoter activity. Supershift analysis identified CREB1, JunB, c-Fos, Fra-1, and c-Jun in protein complexes isolated from differentiated rabbit tracheal epithelial cells binding to this site. Our study shows that the Sp1- and CREB/AP-1-like sites act in concert to stimulate transcription of the TGase I gene. The 2.9-kb promoter region could guide expression of specific genes in the granular layer of the epidermis and could be useful in gene therapy.

Animals↗

PubMed1999

On the mechanism of the enhancement of delayed rectifier K+ current by extracellular ATP in guinea-pig ventricular myocytes.

The effects of extracellular adenosine 5'-triphosphate (ATP) on the delayed rectifier K+ current (IK) were studied in guinea-pig ventricular myocytes using the whole-cell voltage-clamp technique. ATP increased IK concentration dependently with a concentration eliciting a half-maximal response of 1.86 microM and a maximal increase of about 1.8-fold. The enhancement of IK developed slowly, the effect reaching a maximum in about 1.6 min after application of ATP. The rank order of agonist potency in enhancing IK was 2-methylthio-ATP>/= ATP>>alpha,beta-methylene-ATP. The ATP response was attenuated in guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS)- loaded cells, but was not affected by pertussis toxin (PTX)-pre-treatment, indicating that a PTX-insensitive G protein is involved in the response. These features are consistent with operation of P2Y-type purinoceptors. ATP produced a further increase in IK stimulated maximally either by isoprenaline (1 microM) through protein kinase A (PKA) or by 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 nM) through protein kinase C (PKC), while 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7, 10 microM) did not affect the ATP response, suggesting that PKA and PKC do not mediate the response. ATP irreversibly enhanced IK in cells loaded with adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS, 5 mM) or okadaic acid (10 microM), a phosphatase inhibitor, suggesting that a phosphorylation step is present after the receptor stimulation. Genistein, an inhibitor of tyrosine phosphorylation, suppressed the ATP response significantly, while daidzein, an inactive analogue of genistein, had little effect on it, although both genistein or daidzein alone decreased IK. It is hypothesized that tyrosine phosphorylation plays a role in the signalling pathway involved in the enhancement of cardiac IK by P2Y-purinergic stimulation.

Adenosine Triphosphate↗

PubMed1999

Effect of L-arginine infusion on systemic and renal hemodynamics in hypertensive patients.

This study was designed to compare the renal endothelial function in patients with essential hypertension and normal renal function with that in hypertensive patients with renal insufficiency. We studied the effects of L-arginine (500 mg/kg intravenously over 30 min) on renal hemodynamics in 30 normotensive control subjects, 32 patients with mild to moderate essential hypertension who had normal renal function, and seven hypertensive patients with renal insufficiency who had a serum creatinine concentration >2.0 mg/mL and a glomerular filtration rate <50 mL/min/1.48 m2. L-Arginine infusion similarly reduced the mean blood pressure between the three groups (normotensive: -9.7% +/- 0.7%, hypertensives with normal renal function: -10.2% +/- 0.8%, and hypertensives with renal insufficiency: -8.2% +/- 1.3%). The L-arginine-induced decrease in renal vascular resistance was smaller in essential hypertensive patients than in normotensive subjects (-11.0% +/- 2.2 v -19.8% +/- 2.1%, P <.05). However, L-arginine had no effect on the renal vascular resistance in hypertensive patients with renal insufficiency (1.6% +/- 4.8%). Urine nitrite/nitrate levels in response to L-arginine significantly increased in the three groups in the following order: patients with renal insufficiency (47% +/- 15%), essential hypertensive patients (87% +/- 10%), and normotensive subjects (129% +/- 12%). The glomerular filtration rate was unaffected by L-arginine in normotensive and essential hypertensive patients (3.1% +/- 2.4% and 4.2% +/- 2.5%), but significantly decreased in hypertensive patients with renal insufficiency (-13.7% +/- 6.1%). These findings suggest that the ability of the L-arginine-nitric oxide-cGMP pathway to relax the renal vascular tone may be impaired in essential hypertensive patients and more markedly blunted in hypertensive patients with renal insufficiency, in parallel with increasing serum creatinine concentrations.

Arginine↗

PubMed1999

Estimation of intradermal disposition kinetics of drugs: I. Analysis by compartment model with contralateral tissues.

PURPOSE: The objectives of dermal application of drugs are not only systemic therapeutic, but also local ones. We would expect its intradermal kinetics to be dependent on its therapeutic purpose. To develop more efficient drugs for local or systemic therapeutics, it will be important to estimate quantitatively the intradermal disposition of drugs applied topically. We tried, therefore, to develop the compartment model to describe the intradermal disposition kinetics after topical application of drugs. METHODS: In vivo percutaneous absorption study for antipyrine, a model compound, was performed using rats with tape-stripped skin, using the assumption that the stratum corneum permeability to drugs would be improved enough not to be a rate-limiting process. RESULTS: To analyze the results obtained, a 4-compartment model, composed of donor cell, viable skin, muscle, and plasma compartments, was applied. Although the fitting lines obtained could describe the concentration-time profiles of antipyrine in each compartment very well, the concentration profiles in the contralateral tissues were extensively overestimated. Therefore, we developed a 6-compartment model which included the viable skin and muscle in the contralateral site, and analysed the concentration-time curve of each compartment. The fitting curves were in good agreement with the experimental data for all the compartments including the contralateral viable skin and muscle, and thus, this model was recognized to be adequate for the estimation of intradermal kinetics after topical application. Judging from the obtained values of clearance from viable skin to plasma and from viable skin to muscle, about 80% of antipyrine penetrated into viable skin, which suggested it was absorbed into circulating blood and 20% was transported to muscle under viable skin. CONCLUSIONS: Pharmacokinetic analysis using the 6-compartment model would be very useful for the estimation of local and systemic availability after topical application of drugs.

Administration, Topical↗

PubMed1999

Daily aerobic exercise improves reactive hyperemia in patients with essential hypertension.

The effects of long-term aerobic exercise on endothelial function in patients with essential hypertension remain unclear. To determine whether endothelial function relating to forearm hemodynamics in these patients differs from normotensive subjects and whether endothelial function can be modified by continued physical exercise, we randomized patients with essential hypertension into a group that engaged in 30 minutes of brisk walking 5 to 7 times weekly for 12 weeks (n=20) or a group that underwent no activity modifications (control group, n=7). Forearm blood flow was measured using strain-gauge plethysmography during reactive hyperemia to test for endothelium-dependent vasodilation and after sublingual nitroglycerin administration to test endothelium-independent vasodilation. Forearm blood flow in hypertensive patients during reactive hyperemia was significantly less than that in normotensive subjects (n=17). Increases in forearm blood flow after nitroglycerin were similar between hypertensive and normotensive subjects. Exercise lowered mean blood pressure from 115.7+/-5.3 to 110.2+/-5.1 mm Hg (P<0.01) and forearm vascular resistance from 25.6+/-3.2 to 23. 2+/-2.8 mm Hg/mL per minute per 100 mL tissue (P<0.01); no change occurred in controls. Basal forearm blood flow, body weight, and heart rate did not differ with exercise. After 12 weeks of exercise, maximal forearm blood flow response during reactive hyperemia increased significantly, from 38.4+/-4.6 to 47.1+/-4.9 mL/min per 100 mL tissue (P<0.05); this increase was not seen in controls. Changes in forearm blood flow after sublingual nitroglycerin administration were similar before and after 12 weeks of exercise. Intra-arterial infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine abolished the enhancement of reactive hyperemia induced by 12 weeks of exercise. These findings suggest that through increased release of nitric oxide, continued physical exercise alleviates impairment of reactive hyperemia in patients with essential hypertension.

Analysis of Variance↗

PubMed1999

Cloning and characterization of KPL2, a novel gene induced during ciliogenesis of tracheal epithelial cells.

To identify genes upregulated during the process of ciliated cell differentiation of airway epithelial cells, differential display was used to compare RNA from rat tracheal epithelial (RTE) cells cultured under conditions that inhibit/promote ciliated cell differentiation. Several partial complementary DNAs (cDNAs) were identified whose expression was regulated coordinately with ciliated cell differentiation. One of these, KPL2, detected a messenger RNA transcript of approximately 6 kb when used as a probe on Northern blots of RNA from ciliated cultures but was undetectable in RNA from nonciliated cultures. Sequencing of overlapping clones obtained by a modified rapid amplification of cDNA ends procedure generated a complete cDNA sequence that exhibited no significant homology to sequences in GenBank, indicating that KPL2 is a novel gene. Southern analysis demonstrated that KPL2 exists as a single-copy gene. KPL2 contains a long open reading frame predicted to code for a protein of > 200 kD. Several putative functional motifs are present in the protein, including a calponin homology domain, three nuclear localization signals, a consensus P-loop, and a proline-rich region, suggesting that KPL2 has a unique function. KPL2 was undetectable in heart and liver samples, but was expressed in brain and testis, tissues that contain axonemal structures. In seminiferous tubules of the testis, KPL2 expression was stage-specific and appeared to be highest in spermatocytes and round spermatids. During differentiation of RTE cells, the expression of KPL2 closely paralleled that of an axonemal dynein heavy chain. These results suggest that KPL2 plays an important role in the differentiation or function of ciliated cells in the airway.

Amino Acid Sequence↗

PubMed1999

Hyperimmunoglobin E syndrome: a sign of TH1/TH2 imbalance?

We report on a patient with hyperimmunoglobulin E syndrome, who developed pruritic vesiculopapules from the age of six months and also had recurrent episodes of skin abscesses and oral thrush. Serum IgE was extremely elevated at 59,514 IU/ml and specific IgE antibody to Staphylococcus aureus was positive. Histological examination from a vesiculopapule on the face revealed that eosinophil-rich infiltration involved hair follicles, similar to eosinophilic pustular folliculitis. We also examined cytokine profiles of circulating CD4+ T cells by intracellular cytokine staining and flow cytometry. The ratio of cells positive for interferon-gamma was significantly reduced compared with a control. Several reports have shown decreased interferon-gamma production by peripheral blood mononuclear cells of patients with hyperimmunoglobulin E syndrome. We think that this cytokine profile and the histological findings of our patient support the hypothesis that TH1/TH2 imbalance is involved in hyperimmunoglobulin E syndrome.

CD4-Positive T-Lymphocytes↗

PubMed1999

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent head and neck cancer].

A late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer.

Adenocarcinoma↗

PubMed1998

Ergonovine-induced alterations in coronary flow velocity preceding onset of occlusive spasm in patients without significant coronary artery stenoses.

This study examined serial changes in coronary flow velocity to elucidate the dynamic change of coronary circulation during coronary spasm. Twenty patients with variant angina and 27 control patients were studied. Coronary flow velocity was monitored using a Doppler guidewire following intracoronary ergonovine administration. In the control group, diastolic flow velocity either did not change or increased slightly in response to ergonovine. However, in patients with variant angina, 2 patterns of flow velocity alterations were observed. In the first pattern, flow initially increased and then suddenly decreased (16 of 20 patients). In the second pattern, flow gradually decreased (3 of 20 patients). In the remaining patient, the coronary flow alteration could not be detected because of branch spasm. When abnormally high flow velocity was defined as a 100% increase in flow after ergonovine administration within 1 minute, and abnormally low flow velocity was defined as a 50% decrease in flow to diagnose variant angina, sensitivities of 35%, 75%, and 85% were noted if flow was measured 1.0, 2.0, and 3.0 minutes after ergonovine administration, respectively. These abnormal flow velocities were observed before ischemic ST changes appeared. In conclusion, in patients with variant angina, characteristic serial changes in coronary flow velocity occur before occlusive spasm. Variant angina may be diagnosed earlier by monitoring flow velocity rather than by monitoring for ischemic electrocardiographic changes.

Aged↗

PubMed1998

Vasomotility and nitric oxide bioactivity of the bridging segments of the left anterior descending coronary artery.

We compared bridging and nonbridging coronary artery segments with respect to the vasoconstrictor effect of acetylcholine. Bridging segments were hypersensitive to the constrictor effect of acetylcholine, and results suggest that the effect of nitric oxide on the acetylcholine-stimulated condition is decreased, or that the smooth muscle sensitivity to acetylcholine is increased.

Acetylcholine↗

PubMed1998

[Surgical treatment of total anomalous pulmonary venous connection--clinical aspects of pulmonary venous obstruction].

During November 1986 and May 1997, 19 patients with total anomalous pulmonary venous connection (TAPVC) underwent repair surgery. 20 operations including two reoperations were performed. 8 of 19 patients were classified as Darling type Ia, 5 as type IIa, 4 as type III and 2 patients were type IV. Two patients were operated under emergency circumstances within 24 hours after admission, 7 patients were after a short term stabilization of 4.4 days, and the other 11 patients received surgical treatment after a mean of 8.8 days as scheduled cases. For the anostomosis, the common pulmonary venous chamber or the vertical vein was connected with the left atrium in type Ia and III cases; in type IIa and IV cases the cut-back method was performed. Persistent pulmonary hypertension and post-operative pulmonary venous obstruction (PVO) affected the post-operative clinical course. Persistent pulmonary hypertension caused the death of one patient with type IIa and III each, just after operation. One type IV patient died 50 days after operation. The autopsy revealed post-operative obstructions of the remote parts of the pulmonary veins on the anostomosis site. Two patients (type IIa, III) successfully underwent reoperation due to PVO. Post-operative cardiac catheterization was performed after 12 month in 12 cases. Persistent pulmonary hypertension was found in 4 patients, and a type III patient was reoperated because of stenosis of the anostomosis site. The other three patients had persistent pulmonary hypertension without any demonstrable PVO. Persistent pulmonary hypertension and PVO are combined as TAPVC complex. The difficulty to reoperated patients with persistent pulmonary hypertension caused by PVO is one major problem. So preoperative prevention of PVO by normalization the morphologic changes of the pulmonary veins by using drugs could be a different view point in TAPVC therapy after the initial operation.

Anastomosis, Surgical↗

PubMed1998

DD genotype of the angiotensin I-converting enzyme gene is a risk factor for early onset of essential hypertension in Japanese patients.

Although angiotensin-converting enzyme (ACE) plays an important role in blood pressure regulation, no relationship between the insertion/deletion (I/D) polymorphism of the ACE gene and essential hypertension has been observed. However, as the pathogenesis and genetic background of essential hypertension are heterogeneous, we investigated whether the ACE gene is a marker of subgroups of patients with essential hypertension. A group of 178 patients with essential hypertension (90 men/88 women; 53 +/- 13 years of age, mean age +/- SD ) and 101 normotensive control subjects (54 men/47 women; 51 +/- 14 years of age, mean age +/- SD ) were included in the study. The allele frequencies of the two groups were similar. There were no differences in age, blood pressure, retinopathy grade, presence of proteinuria, or resting plasma renin activity (PRA) among the hypertensive patients with the II, ID, and DD genotypes. However, the age of onset of hypertension of patients with the DD genotype was lower (p < 20.05) and their left ventricular mass index was higher (p < 2 0.05) than those in patients with the non-DD genotype. These data suggest that the I/D polymorphism of the ACE gene is associated with an early onset of hypertension and left ventricular hypertrophy in Japanese patients with essential hypertension.

Adult↗

PubMed1998

Dependency on atrial electrophysiological properties of appearance of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome: evidence from atrial vulnerability before and after radiofrequency catheter ablation and surgical cryoablation.

The pathogenesis of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome and the effects of elimination of accessory pathways on the appearance of atrial fibrillation are still controversial. Fifty-four patients with Wolff-Parkinson-White syndrome were classified into three groups: a No AF group (n = 24), patients without paroxysmal atrial fibrillation; an RF-AF Group (n = 12), patients with paroxysmal atrial fibrillation whose accessory pathways were eliminated using radiofrequency catheter ablation; and a Cryo-AF Group (n = 18), patients with paroxysmal atrial fibrillation whose accessory pathways were eliminated with surgical cryoablation. The electrophysiological characteristics of each group were evaluated prior to and following the elimination of their accessory pathways. As indices of atrial vulnerability, the presence of fragmented atrial activity and repetitive atrial firing zones were assessed. Inducibility of atrial fibrillation was significantly reduced following ablation of accessory pathways in the Cryo-AF group (83.3%-5.6%, P < 0.0001), while it was unchanged in the RF-AF group (83.3%-75%). In preablation studies, the effective refractory periods of the atrium in the RF-AF group and the Cryo-AF group were significantly shorter compared with the No AF group (204 +/- 18 ms, 197 +/- 16 ms vs 246 +/- 44 ms, respectively, P < 0.0001). Following ablation, the effective refractory period for patients in the Cryo-AF group was significantly prolonged compared with before ablation (197 +/- 16 ms to 232 +/- 24 ms, P < 0.0001). As a result of this prolongation of the effective refractory period of the atrium, the fragmented atrial activity and repetitive atrial response zones narrowed following ablation in the Cryo-AF group, but not in the RF-AF group. Therefore, the pathogenesis of atrial fibrillation in patients with Wolff-Parkinson-White syndrome may depend on the refractory period of the atrium rather than on the presence of accessory pathways.

Adult↗

PubMed1998

Increased cytosolic free Mg2+ and Ca2+ in platelets of patients with vasospastic angina.

This study was designed to test the hypothesis that the cellular metabolism of Ca2+ and Mg2+, which is important in platelet function, is abnormal in the platelets of patients with vasospastic angina. Cytosolic free Mg2+ concentration ([Mg2+]i) and Ca2+ handling were determined in the platelets of 24 patients with vasospastic angina and 24 control subjects by use of mag-fura 2 and fura 2. Platelet aggregation was also examined. Basal [Mg2+]i and cytosolic free Ca2+ concentration ([Ca2+]i) in platelets were significantly higher in patients with vasospastic angina than in control subjects. The amplitude of the [Ca2+]i transient induced by thrombin (0.03-1.0 U/ml) was significantly increased in the presence, but not in the absence, of extracellular Ca2+ in patients with vasospastic angina, as compared with controls. Therefore, the influx of Ca2+ across the plasma membrane may be accelerated in vasospastic angina. Thrombin (0.1-1.0 U/ml)-induced maximum aggregation response was significantly greater in patients with vasospastic angina than in controls. Results suggest that increased [Mg2+]i and altered Ca2+ handling by platelets may be associated with coronary vasospasm.

Adenosine Diphosphate↗

PubMed1998

Abnormal platelet Ca2+ handling accompanied by increased cytosolic free Mg2+ in essential hypertension.

To test the hypothesis that abnormal platelet Ca2+ handling in essential hypertension results from cellular Mg2+ deficiency, cytosolic free Mg2+ concentration ([Mg2+]i) and Ca2+ metabolism were studied in mag-fura 2 and fura 2-loaded platelets from 30 essential hypertensive patients and 30 sex- and age-matched normotensive controls. Basal cytosolic free Ca2+ concentration ([Ca2+]i) and intracellular Ca2+ discharge capacity were higher in hypertensives than in normotensives (22 +/- 5 vs. 18 +/- 5 nM, P < 0.05; 743 +/- 250 vs. 624 +/- 144 nM, P < 0.05, respectively). The thrombin (0. 03-1.0 U/ml)-evoked [Ca2+]i response was also enhanced in platelets from hypertensives in both the absence and presence of extracellular Ca2+. However, basal [Mg2+]i was higher in hypertensives than in normotensives (437 +/- 110 vs. 353 +/- 85 microM, P < 0.05), whereas serum Mg2+ was similar in the two groups. These results oppose the Mg2+ deficiency hypothesis in platelets in essential hypertension.

Blood Platelets↗

PubMed1998

Physiological control of a total artificial heart: conductance- and arterial pressure-based control.

To obtain a physiological response by a total artificial heart (TAH), while eliminating the hemodynamic abnormalities commonly observed with its use, we proposed the use of a conductance- and arterial pressure-based method (1/R control) to determine TAH cardiac output. In this study, we endeavored to make use of a variable more closely tied to central nervous system (CNS) efferents, systemic conductance, to provide the CNS with more direct control over the output of the TAH. The control equation that calculates the target cardiac output of the TAH was constructed on the basis of measurement of blood pressures and TAH flow. The 1/R control method was tested in TAH-recipient goats with an automatic method by using a microcomputer. In 1/R control animals, the typical TAH pathologies, such as mild arterial hypertension and substantial systemic venous hypertension, did not occur. Cardiac output varied according to daily activity level and exercise in a manner similar to that observed in natural heart goats. These results indicate that we have determined a control method for the TAH that avoids hemodynamic abnormalities exhibited by other TAH control systems and that exhibits physiological responses to exercise and daily activities under the conditions tested. The stability of the control and the complete lack of inappropriate excursions in cardiac output is suggestive of CNS involvement in stabilizing the system.

Animals↗

PubMed1998

Effect of 17beta-estradiol on inhibition of platelet aggregation in vitro is mediated by an increase in NO synthesis.

The low prevalence of coronary heart disease in premenopausal women and its increase after menopause are well established. Although estrogen is thought to play a role in protecting the vasculature, the mechanism has not been fully clarified. The contribution of platelets to atherosclerotic cardiovascular diseases is well recognized. The present study focused on the still-controversial effect of estrogen on platelet function. We investigated the in vitro effects of estrogen on human platelets, including their aggregation, Ca2+ metabolism, the synthesis of cyclic nucleotides, and NO (nitrite/nitrate) synthesis after stimulation with thrombin or ADP. Pretreatment of platelets with 17beta-estradiol reduced the platelet aggregation induced by thrombin or ADP, whereas 17alpha-estradiol had no effect. 17Beta-estradiol accelerated the recovery of [Ca2+]i after the agonist-induced peak and reduced the area under the curve of accumulated platelet [Ca2+]i but did not alter the baseline [Ca2+]i, Ca2+ influx induced by thrombin or ADP, the release of Ca2+ from internal stores, or the size of internal Ca2+ stores. Pretreatment of platelets with 17beta-estradiol had no effect on the intracellular concentration of cAMP but increased that of cGMP in agonist-stimulated platelets. Additionally, 17beta-estradiol increased the platelet concentration of nitrite/nitrate in a dose-dependent manner. These effects of 17beta-estradiol on platelet aggregation, Ca2+ metabolism, and NO synthesis were abolished by exposure to N(G)-monomethyl-L-arginine, an NO synthesis inhibitor. These results suggest that 17beta-estradiol plays an important role in inhibiting platelet aggregation by promoting Ca2+ extrusion or reuptake activity that is dependent on the production of cGMP by increasing NO synthesis.

Adult↗