Biomedical subjects

M Kakihana

Publications and source records attributed to M Kakihana.

At least 19 recordsLinked to original sources

PubMed2005

Neutron powder diffraction study of Pb(HfxTi1-x)O3 ceramics (0.10<or=x<or=0.50).

The crystal symmetries of lead hafnate titanate (Pb(HfxTi1-x)O3, PHT) powders with 0.10<or=x<or=0.50 were investigated by high-resolution neutron powder diffraction. Samples with x<or=0.40 were tetragonal (space group P4 mm), while the sample with x=0.50 contained both monoclinic Cm and rhombohedral (modeled using the R3c space group) phases. The role of the B cations (Hf and Ti) and the oxygen octahedra network, in addition to the displacement of Pb ions from their ideal sites, in promoting the phase transformation between the P4 mm and Cm phases was considered. Two types of structural disorder were identified. Diffuse scattering between Bragg reflection peaks was assigned to Pb ion displacement. A second type of structural disorder, revealed by the weak intensities of observed pseudo-cubic 00l reflections with l even and as 00l reflection peak widths significantly broader than the l00 reflection peaks, was observed. This behavior was attributed to disorder in the arrangement of the O-B-O rows parallel to the c axis. For small values of x, this shift was predominantly along the c axis, whereas shifts perpendicular to the c axis increased with increasing x. These features were modeled using an hkl-dependent line-broadening model. The origin of the hkl-dependent line broadening was assigned to the microstrain accompanying a spatial-composition variation. Structural models were tested by computing valence sums and spontaneous polarization values.

Journal Article↗

PubMed2004

Chelating of titanium by lactic acid in the water-soluble diammonium tris(2-hydroxypropionato)titanate(IV).

Stable water-soluble diammonium tris(2-hydroxypropionato)titanate(IV) [ammonium trilactatotitanate(IV)], (NH4)2[Ti(C3H4O3)3], was prepared in the crystalline form. According to the X-ray single-crystal diffraction data, this compound crystallizes in the cubic cell with a = 11.649(4) angstroms, space group P2(1)3 (no. 198), and has Z = 4 molecules per unit cell. The 13C NMR data and Raman and IR spectra support the determined structure. The absence of nonbonded functional groups restricts the formation of oligomers in contrast to the reported speciation of citratoperoxotitanate(IV) complexes.

Chelating Agents↗

PubMed2001

In situ telomerase activity in pleural effusions: a promising marker for malignancy.

Telomerase activity in 16 pleural effusions was studied using an in situ telomerase repeat amplification protocol (TRAP) assay on cytospin preparations. Six of nine cytologically malignant specimens contained telomerase-positive cells (67%), and in two further specimens, suspicious positive cells were seen. Two of four atypical specimens contained telomerase-positive cells, whereas two benign cases were telomerase-negative. No mesothelial cells showed telomerase reactivity. Thus, telomerase activity was specific for malignancy and it was always found only in malignant cells. The results suggest that telomerase activity measured with this in situ method can be a valuable complement in the assessment of malignancy in pleural effusions.

Biomarkers, Tumor↗

PubMed2001

Guinea pig histamine N-methyltransferase: cDNA cloning and mRNA distribution.

We report here the isolation of histamine N-methyltransferase (HMT) cDNA from the guinea pig brain by the polymerase chain reaction on the basis of nucleotide sequences of rat and human counterparts. Guinea pig HMT consists of 292 amino acids, with homologies of 75.6% and 79.1% to rat and human HMT, respectively. Northern blotting analysis indicated that the 1.6-kb guinea pig HMT transcript was expressed at various levels in different tissues at the following relative abundance: jejunum, brain > lung, spleen, stomach > liver, kidney. HMT mRNA localized throughout the jejunum, and it was mainly expressed in epithelial cells and in Auerbach's plexus.

Amino Acid Sequence↗

PubMed2000

Correlation between morphology and telomerase activity in cells from exfoliative lung cytologic specimens.

BACKGROUND: Telomerase is a ribonucleoprotein that compensates for the erosion of telomeres (chromosomal termini). Telomerase activity is detected in more than 85% of cancerous lesions and is therefore considered a novel marker of cancer. The authors compared cytologic morphology and telomerase activity at the cellular level to obtain further insight into their association. METHODS: The authors used bronchial washing and brushing materials obtained from 18 patients with lung carcinomas (6 squamous cell, 8 adenocarcinoma, 2 large cell, 1 small cell, and 1 metastasis from colon carcinoma) and 20 patients with nonmalignant disease. An in situ telomeric repeat amplification protocol (TRAP) assay was performed, and routine Papanicolaou-stained slides using the same sample were assessed. RESULTS: Nuclear fluorescent signals at the nuclear area, corresponding to telomerase activity, shown by the in situ TRAP assay were only detected in samples containing morphologically malignant cells. No nuclear fluorescence was seen in the keratinizing component of well-differentiated squamous cell carcinoma. Nuclear staining was not seen in metaplastic or basal hyperplastic cells. Cytoplasmic fluorescence was only found in macrophages and polymorphonuclear leukocytes. CONCLUSIONS: Nuclear fluorescence corresponding to telomerase activity was not demonstrated in metaplastic or basal hyperplastic cells, thus indicating that detection of telomerase activity is closely associated with the presence of malignant cells, but not premalignant lesions, in lung carcinoma patients. Moreover, in some samples with cancer, cells failed to show telomerase activity, suggesting the limitation of this method for the detection of malignant cells in certain lung carcinoma patients.

Adenocarcinoma↗

PubMed2000

[Bronchofiberscopy].

New diagnostic modalities have been used in conjunction with endoscopy for early detection of lung cancer. Videoendoscope is routinely used instead of fiberoptic bronchoscope. Fluorescence diagnosis has been proved to be useful in detecting subtle lesions which might be invisible by conventional endoscopy in central airway. Also, a number of small peripheral lesions has increased by the helical CT. CT guided transbronchial lung as well as needle cytology are indicated for definitive diagnosis of such lesions. Endobronchial Ultrasonography is employed to evaluate the depth of cancer invasion of the bronchus and lymph node swelling around the bronchus. It should be helpful in staging of lung cancer and selecting therapy.

Bronchoscopy↗

PubMed2000

[Molecular biological diagnosis].

Biological behavior of lung cancer was evaluated by basic study. Malignancy Associated Change is the concept that the nuclear features of normal cells in the vicinity of cancer show subtle morphological difference from those of healthy individuals. The difference was recognized by high resolution cytometry and the expression of MAC cells was correlated with the degree of abnormality of chest diseases. Comparative genomic hybridization and fluorescence in situ hybridization were performed to investigate genetic abnormality of. Multiple genetic abnormalities and chromosomal instability showed poor prognosis. Two dimensional electrophoresis was employed to detect the expression of the specific protein of lung cancer. TAO2 was proved to be specific to well differentiated adenocarcinoma. Also, metabolic analysis will be employed for cell analysis.

Biomarkers, Tumor↗

PubMed1999

The relationship between p21/waf1 expression patterns and cell proliferation during the tumorigenesis of the bronchus.

Each developmental stage in the process towards bronchial squamous cell carcinoma (normal epithelium, squamous metaplasia and early stage squamous cell carcinoma including in situ carcinoma) was examined for p21/waf1 protein expression and cell proliferation using MIB1. P21/waf1 immunoreactivity was classified into four patterns: predominantly cytoplasmic staining, exclusively nuclear staining, both nuclear and cytoplasmic staining and negative. The cases with predominantly cytoplasmic staining showed suppression of cell proliferation. Most cases with either negative or exclusively nuclear staining revealed high cell proliferation. The simultaneous evaluation of p21/waf1 and cell proliferation is valuable for clinical determination of the high risk for malignant transformation.

Blotting, Western↗

PubMed1998

Randomized, double-blind, placebo-controlled study of ascorbate on the preventive effect of nitrate tolerance in patients with congestive heart failure.

BACKGROUND: Reduced cGMP production caused by increased superoxide has been proposed as a mechanism of nitrate tolerance during continuous nitrate therapy. This study was designed to evaluate the effects of ascorbate, an antioxidant, on the development of nitrate tolerance during continuous nitrate therapy in patients with congestive heart failure. METHODS AND RESULTS: Twenty patients with congestive heart failure were randomized to receive intravenous infusion of nitroglycerin concomitantly with placebo (placebo group, n=10) or intravenous ascorbate (vitamin C group, n=10). After baseline measurements were obtained, dose titration was started by the infusion of nitroglycerin at a rate of 0.5 microg/kg per minute (titration period). Measurements of hemodynamic parameters and blood sampling were performed serially at 0, 6, 12, 18, and 24 hours after the titration period. At baseline, mean pulmonary artery pressure (MPAP, mm Hg), mean pulmonary capillary wedge pressure (PCWP, mm Hg), plasma vitamin E level (micromol/L), and platelet cGMP level (pmol/10[9] platelets) were comparable in the two groups (placebo group: MPAP, 48+/-6; PCWP, 24+/-4; cGMP, 0.76+/-0.12; vitamin E, 18.2+/-1.2; vitamin C: MPAP, 49+/-7; PCWP, 24+/-4; cGMP, 0.71+/-0.16; vitamin E, 18.6+/-1.3). In both groups, at 6 hours after the titration period, MPAP and PCWP were significantly decreased (placebo group: MPAP, 26+/-5; PCWP, 15+/-4; vitamin C: MPAP, 26+/-4; PCWP, 16+/-4), and platelet cGMP was significantly increased (placebo group: 2.42+/-0.24; vitamin C: 2.26+/-0.26). However, at 18 hours after titration, in the placebo group, MPAP (44+/-5) and PCWP (23+/-4) were increased, and platelet cGMP (0.85+/-0.20) and plasma vitamin E levels (12.4+/-1.4) were significantly decreased. In contrast, in the vitamin C group, MPAP (31+/-6), PCWP (17+/-5), platelet cGMP (2.49+/-0.23), and plasma vitamin E levels (17.6+/-1.4) were maintained for 18 hours after the titration period. CONCLUSIONS: These findings indicate that ascorbate, an antioxidant, may prevent the development of nitrate tolerance during continuous nitrate therapy in patients with congestive heart failure.

Aged↗

PubMed1998

Randomized, double-blind, placebo-controlled study of the preventive effect of supplemental oral vitamin C on attenuation of development of nitrate tolerance.

OBJECTIVES: This study sought to evaluate the preventive effect of vitamin C, an antioxidant, on the development of nitrate tolerance. BACKGROUND: Decreased intracellular production of cyclic guanosine monophosphate (cGMP) is a mechanism of nitrate tolerance, and increased superoxide levels and reduced activation of guanylate cyclase have been observed in vitro. METHODS: In this double-blind, placebo-controlled study, 24 normal volunteers and 24 patients with ischemic heart disease (IHD) were randomized to receive either vitamin C (2 g three times daily [vitamin C group, n=12]) or placebo (placebo group, n=12). The vasodilator response to nitroglycerin was assessed with forearm plethysmography by measuring the change in FBF before and 5 min after sublingual administration of 0.3 mg of nitroglycerin. Blood samples were simultaneously obtained to measure platelet cGMP levels. FBF was measured, and blood sampling was performed serially at baseline (day 0), 3 days after administration of vitamin C or placebo (day 3) and 3 days after application of a 10-mg/24-h nitroglycerin tape concomitantly with oral vitamin C or placebo (day 6). RESULTS: There were no differences between the vitamin C and placebo groups in percent increases in FBF (%FBF) or platelet cGMP levels (%cGMP) after administration of sublingual nitroglycerin on day O (%FBF: normal volunteers 31+/-8 vs. 32+/-10; patients with IHD 32+/-9 vs. 32+/-8; %cGMP: normal volunteers 37+/-9 vs. 39+/-10; patients with IHD 38+/-10 vs. 39+/-10 [vitamin C group vs. placebo group]) or day 3 (%FBF: normal volunteers 32+/-9 vs. 33+/-9; patients with IHD 31+/-10 vs. 31+/-10; %cGMP: normal volunteers 36+/-8 vs. 37+/-9; patients with IHD 39+/-11 vs. 38+/-10 [vitamin C group vs. placebo group]). The %FBF and %cGMP in the placebo group were significantly lower on day 6 than in the vitamin C group (%FBF: normal volunteers 30+/-8 vs. 19 4, p < 0.01; patients with IHD 29+/-9 vs. 17+/-6, p < 0.01; %cGMP: normal volunteers 36 10 vs. 17+/-6, p < 0.01; patients with IHD 37+/-11 vs. 15+/-5, p < 0.01 [vitamin C group vs. placebo group]). CONCLUSIONS: These results indicate that combination therapy with vitamin C is potentially useful for preventing the development of nitrate tolerance.

Adult↗

PubMed1998

Randomized, double-blind, placebo-controlled study of carvedilol on the prevention of nitrate tolerance in patients with chronic heart failure.

OBJECTIVES: This study was designed to evaluate the effect of carvedilol on nitrate tolerance in patients with chronic heart failure. BACKGROUND: The attenuation of cyclic guanosine 5'-monophosphate (cGMP) production due to inactivation of guanylate cyclase by increased superoxide has been reported as a mechanism of nitrate tolerance. Carvedilol has been known to combine alpha/beta-blockade with antioxidant properties. METHODS: To evaluate the effect of carvedilol on nitrate tolerance, 40 patients with chronic heart failure were randomized to four groups that received either carvedilol (2.5 mg once a day [carvedilol group, n=10]), metoprolol (30 mg once a day [metoprolol group, n=10]), doxazosin (0.5 mg once a day [doxazosin group, n=10]) or placebo (placebo group, n=10). Vasodilatory response to nitroglycerin (NTG) was assessed with forearm plethysmography by measuring the change in forearm blood flow (FBF) before and 5 min after sublingual administration of 0.3 mg NTG, and at the same time blood samples were taken from veins on the opposite side to measure platelet cGMP. Plethysmography and blood sampling were obtained serially at baseline (day 0); 3 days after carvedilol, metoprolol, doxazosin or placebo administration (day 3); and 3 days after application of a 10-mg/24-h NTG tape concomitantly with carvedilol, metoprolol, doxazosin or placebo (day 6). RESULTS: There was no significant difference in the response of FBF (%FBF) and cGMP (%cGMP) to sublingual NTG on day 0 and day 3 among the four groups. On day 6, %FBF and %cGMP were significantly lower in the metoprolol, doxazosin and placebo groups than on day 0 and day 3, but these parameters in the carvedilol group were maintained. CONCLUSIONS: These results indicated that carvedilol may prevent nitrate tolerance in patients with chronic heart failure during continuous therapy with NTG.

Adrenergic Antagonists↗

PubMed1998

Preventive effects of carvedilol on nitrate tolerance--a randomized, double-blind, placebo-controlled comparative study between carvedilol and arotinolol.

OBJECTIVES: This study was designed to compare the preventive efect of nitrate tolerance between carvedilol with antioxidant properties and arotinolol without antioxidant properties. BACKGROUND: The attenuation of cyclic guanosine monophosphate (cGMP) production due to inactivation of guanylate cyclase by increased superoxide has been reported as a mechanism of nitrate tolerance. Carvedilol has been known to combine alpha- and beta-blockade with antioxidant properties. METHODS: To evaluate the preventive effect of nitrate tolerance, 24 patients with untreated hypertension were randomized to receive either carvedilol (10 mg twice a day [carvedilol group, n=8]), arotinolol (10 mg twice a day [arotinolol group, n=8]), or placebo (placebo group, n=8). Vasodilatory response to nitroglycerin (NTG) was assessed with forearm plethysmography by measuring the change in forearm blood flow (FBF) before and 5 min after sublingual administration of 0.3 mg NTG, and at the same time blood samples were taken from veins on the opposite side to measure platelet cGMP. Plethysmography and blood sampling were obtained serially at baseline (day 0), 3 days after carvedilol, arotinolol or placebo administration (day 3) and 3 days after application of a 20 mg/24 h NTG tape concomitantly with carvedilol, arotinolol or placebo (day 6). RESULTS: There was no significant difference in the response of FBF (%FBF) and cGMP (%cGMP) to sublingual administration of NTG on days 0 and 3 among the three groups. On day 6, %FBF and %cGMP were significantly lower in the arotinolol group and the placebo group than days 0 and 3, but these parameters in the carvedilol group were maintained. CONCLUSIONS: The results indicated that carvedilol with antioxidant properties may prevent the development of nitrate tolerance during continuous therapy with NTG compared with arotinolol without antioxidant properties.

Adrenergic Antagonists↗

PubMed1998

Preventive effects of angiotensin-converting enzyme inhibitors on nitrate tolerance during continuous transdermal application of nitroglycerin in patients with chronic heart failure.

This study was designed to investigate the effect of angiotensin-converting enzyme (ACE) inhibitors with and without a sulfhydryl group on intracellular production of cGMP, forearm blood flow, and neurohormonal factors during continuous transdermal application of nitroglycerin in patients with chronic heart failure. Platelet cGMP level and forearm blood flow were measured before and 5 min after sublingual administration of nitroglycerin (NTG) in 20 patients with chronic heart failure during the following 4 phases: (1) baseline phase; (2) NTG phase (1 week after NTG tape 10 mg/day); (3) CPT phase (1 week after both captopril 37.5 mg/day and NTG tape 10 mg/day); and (4) ENL phase (1 week after both enalapril 5 mg/day and NTG tape 10 mg/day). The platelet GMP level before sublingual NTG and forearm blood flow were significantly higher during the 3 phases with NTG tape than during the control phase. The percent increases in platelet cGMP level and forearm blood flow after sublingual NTG were significantly lower during the NTG phase than during the baseline phase. In contrast, concomitant application of ACE inhibitors maintained the percent increase in platelet cGMP level and forearm blood flow. These results indicate that concomitant therapy with ACE inhibitors may be helpful in preventing the attenuation of intracellular cGMP production in patients with chronic heart failure during continuous transdermal application of NTG.

Administration, Cutaneous↗

PubMed1998

Efficacy and rebound phenomenon related to intermittent nitroglycerin therapy for the prevention of nitrate tolerance.

Intermittent transdermal therapy of nitroglycerin (NTG) has been recommended for the prevention of nitrate tolerance, but a rebound phenomenon has been reported to occur following removal of the NTG tape. The present study investigated the effects of intermittent NTG therapy on vasodilatory response and the intracellular production of cyclic GMP (cGMP). The study group comprised 12 healthy adults and measurements were taken of the platelet cGMP level, the venous volume (VV) (by forearm plethysmography) and the plasma levels of neurohormonal factors before and 5 min after administration of 0.3 mg of sublingual nitroglycerin (NTG) during the following 4 phases: (i) the control phase (8.00 h); (ii) the continuous phase (8.00 h; 7 days after continuous application of a 10 mg/24 h NTG tape); (iii) the intermittent application phase (8.00 h; 7 days after intermittent application of NTG tape, applied at 21.00 h and removed at 9.00 h); and (iv) the intermittent removal phase (13.00 h; 4 h after removal of the NTG tape in the intermittent phase). The percentage increase in cGMP (%cGMP) and venous volume (%VV) were significantly lower in the continuous phase than the control phase, but there was no difference between the control and the intermittent application phases. However, in the intermittent removal phase, the cGMP level before sublingual NTG, the %cGMP and the %VV were unchanged, but the VV before sublingual NTG was significantly lower than in the control phase. Plasma renin activity and the plasma level of angiotensin II were significantly increased in the continuous phase, the intermittent application phase, and the intermittent removal phase. In conclusion, intermittent transdermal NTG therapy prevented nitrate tolerance in the production of cGMP and vasodilation, but induced a rebound phenomenon after removal of the NTG tape. The rebound phenomenon following the tape removal may be related to some other mechanism, such as activation of neurohormonal factors.

Administration, Cutaneous↗

PubMed1998

[Randomized, double-blind, placebo-controlled study of supplemental vitamin E on attenuation of the development of nitrate tolerance].

The attenuation of intracellular production of cyclic guanosine monophosphate (cGMP) has been known as a mechanism of nitrate tolerance. A recent in vitro study have shown an increase in superoxide levels and a reduced activation of guanylate cyclase in tolerant vessels. We investigated the preventive effect of an antioxidant, vitamin E, on the development of nitrate tolerance. In this double-blind, placebo-controlled study, 24 normal volunteers and 24 patients with ischemic heart disease (IHD patients) were randomized to receive either vitamin E (200 mg t. i. d.; vitamin E group) or placebo (placebo group). Vasodilator response to nitroglycerin was assessed with forearm plethysmography by measuring the change in the forearm blood flow before and 5 min after sublingual administration of 0.3 mg nitroglycerin, and at the same time, blood samples were taken from veins to measure the platelet cGMP level. Measurements of the forearm blood flow and blood sampling were obtained serially at baseline (day 0), 3 days after taking vitamin E or placebo alone (day 3), and 3 days after application of a 10 mg/24 hr nitroglycerin tape concomitantly with oral vitamin E or placebo (day 6). The response of forearm blood flow (%FBF) and cGMP (%cGMP) after sublingual nitroglycerin on day 0(%FBF: normal volunteers 32 +/- 12% vs 31 +/- 11%, IHD patients 35 +/- 15% vs 34 +/- 15%; %cGMP: normal volunteers 38 +/- 10% vs 35 +/- 11%, IHD patients 37 +/- 11% vs 38 +/- 12%; vitamin E group as placebo group) and day 3(%FBF: normal volunteers 33 +/- 9% vs 32 +/- 12%, IHD patients 35 +/- 12% vs 33 +/- 13%, %cGMP: normal volunteers 38 +/- 10% vs 37 +/- 11%, IHD patients 36 +/- 14% vs 37 +/- 10%, vitamin E group vs placebo group) were not different between the two groups. On day 6 %FBF and %cGMP in the placebo group were significantly lower compared with day 0, and there were significant differences in them between the two groups (%FBF: normal volunteers 30 +/- 12% vs 17 +/- 9%, p < 0.01; IHD patients 28 +/- 14% vs 17 +/- 8%, p < 0.01; %cGMP: normal volunteers 35 +/- 11% vs 8 +/- 5%, p < 0.01; IHD patients 38 +/- 10% vs 12 +/- 4%, p < 0.01, vitamin E group vs placebo group). In conclusion, the combination therapy with vitamin E is potentially a useful method to prevent the development of nitrate tolerance.

Aged↗

PubMed1997

The novel compound TDN-345 induces synthesis/secretion of nerve growth factor in C6-10A glioma cells.

A novel compound, TDN-345, not bearing catechol moiety, induced NGF synthesis/secretion in C6-10A glioma cells. Both intracellular and extracellular nerve growth factor (NGF) protein levels increased within 3 h and reached a maximum around 12 h after the addition of TDN-345. The induction of NGF synthesis/secretion by TDN-345 occurred in a concentration-dependent manner, beginning with about 0.1 microM and reaching a maximum at 10 microM. The ED50 was 0.88 microM. The induction was accompanied by an increase in NGF mRNA but not beta-actin mRNA. In a time-course study, the NGF mRNA level was found to reach a maximum 2-3 h after the addition of TDN-345 and then to return to control levels. The induction occurred dose-dependently. The catecholaminergic compound epinephrine, which induces NGF synthesis/secretion, increased the intracellular cyclic AMP content by more than 1000-times at 10 microM. In contrast, TDN-345 did not cause such a prominent increase in cAMP even at 100 microM. These results indicate that TDN-345 induces NGF synthesis/secretion by increasing NGF mRNA expression, and the action of TDN-345 clearly differs from that of epinephrine, as it does not seem to involve cAMP as a second messenger. The results of the present study suggest the existence of a signal transduction pathway for NGF synthesis/secretion which is not mediated by cAMP.

Animals↗

PubMed1997

Randomized, double-blind, placebo-controlled study of supplemental vitamin E on attenuation of the development of nitrate tolerance.

BACKGROUND: The attenuation of intracellular production of cGMP has been known to be a mechanism of nitrate tolerance. A recent in vitro study showed an increase in superoxide levels and a reduced activation of guanylate cyclase in tolerant vessels. We investigated the preventive effect of an antioxidant, vitamin E, on the development of nitrate tolerance. METHODS AND RESULTS: In this double-blind, placebo-controlled study, 24 normal volunteers and 24 patients with ischemic heart disease (IHD patients) were randomized to receive either vitamin E (200 mg TID vitamin E group) or placebo (placebo group). Vasodilator response to nitroglycerin was assessed with forearm plethysmography by measurement of the change in the forearm blood flow before and 5 minutes after sublingual administration of 0.3 mg nitroglycerin, and at the same time, blood samples were taken from veins to measure the platelet cGMP level. Measurements of the forearm blood flow and blood sampling were obtained serially at baseline (day 0), 3 days after vitamin E or placebo alone was taken (day 3), and 3 days after application of a 10-mg/24-h nitroglycerin tape concomitantly with oral vitamin E or placebo (day 6). The responses of forearm blood flow (%FBF) and cGMP (%cGMP) after sublingual nitroglycerin on day 0 (%FBF: normal volunteers, 32+/-12 versus 31+/-11; IHD patients, 35+/-15 versus 34+/-15; %cGMP: normal volunteers, 38+/-10 versus 35+/-11; IHD patients, 37+/-11 versus 38+/-12, vitamin E group versus placebo group) and day 3 (%FBF: normal volunteers, 33+/-9 versus 32+/-12; IHD patients, 35+/-12 versus 33+/-13; %cGMP: normal volunteers, 38+/-10 versus 37+/-11; IHD patients, 36+/-14 versus 37+/-10, vitamin E group versus placebo group) were not different between the two groups. On day 6, %FBF and %cGMP in the placebo group were significantly lower compared with day 0, and there were significant differences in them between the two groups (%FBF: normal volunteers, 30+/-12 versus 17+/-9, P<.01; IHD patients, 28+/-14 versus 17+/-8, P<.01; %cGMP: normal volunteers, 35+/-11 versus 8+/-5, P<.01; IHD patients, 38+/-10 versus 12+/-4, P<.01, vitamin E group versus placebo group). CONCLUSIONS: These results indicate that the combination therapy with vitamin E is potentially a useful method to prevent the development of nitrate tolerance.

Administration, Oral↗

PubMed1997

Effects of enalapril during continuous nitrate therapy: analysis of diameter of coronary arteries and platelet cyclic guanosine monophosphate.

To investigate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on nitrate tolerance during continuous nitrate therapy, coronary artery diameters and platelet cyclic guanosine monophosphate (cGMP) levels were measured before and 2 minutes after intracoronary injection of nitroglycerin 200 microg in 60 patients with coronary artery disease and were compared among 20 patients treated with nitrates (nitrate group), 20 patients treated with both nitrates and enalapril (enalapril group), and 20 untreated patients (control group). The percent increase in platelet cGMP and coronary dilatation in the nitrate group was significantly less than in the control group, but the percent increase in the enalapril group was significantly greater than that in the nitrate group. These results indicate that enalapril may be helpful as concomitant therapy to maintain the effect of nitrates during continuous nitrate therapy.

Aged↗