Biomedical subjects

K Maeda

Publications and source records attributed to K Maeda.

At least 271 records · Page 15Linked to original sources

PubMed1999

Plasma levels of nitric oxide and related vasoactive factors following long-term treatment with angiotensin-converting enzyme inhibitor in patients with essential hypertension.

Several mechanisms other than the inhibition of systemic and local formation of angiotensin II (Ang II) have been proposed to play a role in mediating the hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors. In the present study, we measured plasma levels of nitric oxide (NO) and the related vasoactive factors bradykinin, 6-keto prostaglandin F1alpha (6-keto PGF1alpha) a stable metabolite of prostacyclin, and cyclic guanosine-3',5'-monophosphate (cGMP) before and after a 4-week treatment with the ACE inhibitor lisinopril in 17 patients with essential hypertension. Plasma NO levels were measured by the Griess method after conversion of nitrate to nitrite. Long-term lisinopril treatment significantly reduced blood pressure and increased plasma NO and 6-keto PGF1alpha. The treatment also tended to increase plasma levels of bradykinin and cGMP, but not to a significant extent. The posttreatment NO level was inversely correlated with posttreatment systolic, diastolic, and mean blood pressure (n = 17, r= -.68, P< .01, n = 17, r= -.54, P < .05, and n = 17, r= -.66, P< .01, respectively). The posttreatment bradykinin level was also modestly correlated with posttreatment systolic and mean blood pressure (n = 17, r = -.51, P < .05 and n = 17, r = -.55, P < .05, respectively). In contrast, posttreatment 6-keto PGF1alpha and cGMP levels were not correlated with posttreatment systolic, diastolic, or mean blood pressure. These findings raise the possibility that increased formation of NO and bradykinin, as well as inhibition of the renin-angiotensin system, contribute to the hypotensive effect of the ACE inhibitor observed in our hypertensive patients.

6-Ketoprostaglandin F1 alpha↗

PubMed1999

Transvaginal Doppler assessment of fetal intracranial venous flow.

OBJECTIVE: To investigate physiologic blood-flow-velocity waveform patterns of the fetal cerebral venous system during normal pregnancies by transvaginal Doppler studies and to evaluate cases with abnormal venous-flow patterns. METHODS: Internal cerebral veins and the three dural sinuses, those of the superior sagittal sinus, vein of Galen, and straight sinus, were examined in normal cephalic-presenting fetuses of 20-40 weeks' gestation. For analysis, the venous index was defined as maximum minus minimum velocity divided by maximum velocity. Different cases with intracranial abnormalities were evaluated with emphasis on abnormal venous blood-flow patterns. RESULTS: Internal cerebral veins had pulsatile patterns with a venous index of 0.22 in 47.6% of fetuses, whereas all fetuses had pulsations in the dural sinuses. The vein of Galen had a significantly lower venous index (0.31) than the superior sagittal sinus (0.39) and the straight sinus (0.36), indicating that the amplitude of the intracranial venous pulsation might increase as the flow runs from the periphery toward the proximal portion. Significant regression lines of venous index were obtained, indicating the stability of the pulsation during pregnancy. A flat pattern of superior sagittal sinus flow was found in three cases of hydrocephalus and one of craniosynostosis. CONCLUSION: We showed the normal patterns of fetal cerebral venous blood-flow velocity and the abnormal patterns which might be associated with increased intracranial pressure. Doppler assessment of the intracranial venous system enabled us to evaluate intracranial abnormalities accompanied by increased intracranial pressure that might have prognostic clinical importance.

Blood Flow Velocity↗

PubMed1999

Effect of metal ions on the stable adduct formation of 16alpha-hydroxyestrone with a primary amine via the Heyns rearrangement.

16alpha-Hydroxyestrone (16alpha-OHE1), one of the major estrogen metabolites in humans that may plays a role in cell transformation, has been found to form stable adducts with nuclear proteins. The mechanism for the formation of a stable covalent adduct of 16alpha-OHE1 with protein has been postulated via the Heyns rearrangement after Schiff base formation. The Heyns rearrangement on the steroidal D-ring alpha-hydroxyimine was investigated using 17-(2-methoxyethylimino)estra-1,3,5(10)-triene-3,16alpha-dio l as a model intermediate. Rates of the Heyns rearrangement and hydrolysis of the steroidal a-hydroxyimine were determined by a high-performance liquid chromatography (HPLC) simultaneously. The Heyns rearrangement was demonstrated to be optimum at pH 6.2 and the reaction rate at physiological pH, 7.3-7.5, was more than 90% of that at the optimum pH. On the other hand, modulator(s) to the reactions were also examined. According to our previous finding of the proton-mediated mechanism of the Heyns rearrangement, the effects of cationic metal ions on the reactions were examined with 29 metal chlorides. Five metal ions, Pt4+, Cu2+, Ni2+, Co2+, and Mn2+, suppressed the formation of Heyns product significantly while Fe2+, Y3+, Gd3+, and Er3+ slightly increased it. The suppression rate was synergistically enhanced by the combination of Pt4+ with Co2+, Cu2+, or Ni2+. These results suggest the five metal ions, Pt4+, Cu2+, Ni2+, Co2+, and Mn2+, reduce the formation of the Heyns product in vivo and, therefore, would be useful tools to clarify the implication of the stable adduct formation of 16alpha-OHE1 with protein.

Cations↗

PubMed1999

Vitrectomy for rhegmatogenous or tractional retinal detachment with familial exudative vitreoretinopathy.

OBJECTIVE: To examine the anatomic features and surgical indications of familial exudative vitreoretinopathy (FEVR) complicated with rhegmatogenous or tractional retinal detachment. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Twenty-eight eyes of 25 patients who had either clinically suspected or fully diagnosed FEVR. Of these, 25 had rhegmatogenous retinal detachment, 2 had tractional retinal detachment, and 1 had tractional retinal detachment plus vitreous hemorrhage. INTERVENTIONS: The authors carefully observed the vitreoretinal interface during surgery, studied the clinical and anatomic features of FEVR, and then evaluated the surgical results. RESULTS: The vitreoretinal adhesions were so strong in the peripheral avascular area that iatrogenic retinal breaks easily occurred in 22 of 28 eyes. In all cases, the bimanual technique with vitreous scissors and forceps was required to dissect the posterior vitreous membrane from the retinal surface. The retina was reattached in 24 of 28 cases (85.7%), and visual acuity improved in 20 eyes (71.4%). CONCLUSION: Dissection of the vitreous in the peripheral avascular area is very difficult in FEVR, and those patients for whom this procedure was not successfully performed may have a poorer prognosis.

Adolescent↗

PubMed1999

Effects of visual and auditory stimulation on somatosensory evoked magnetic fields.

DESIGN AND METHODS: We investigated the effects of continuous visual (cartoon and random dot motion) and auditory (music) stimulation on somatosensory evoked magnetic fields (SEFs) following electrical stimulation of the median nerve on 12 normal subjects using paired t test and two way ANOVA for the statistics. RESULTS: In the hemisphere contralateral to the stimulated nerve, the middle-latency components (35-60 ms in latency) were significantly enhanced by visual, but not by auditory stimulation. The dipoles of all components within 60-70 ms following stimulation were estimated to be very close each other, around the hand area of the primary sensory cortex (SI). In the ipsilateral hemisphere, the middle-latency components (70-100 ms in latency), the dipoles of which were estimated to be in the second sensory cortex (SII), were markedly decreased in amplitude by both the visual and auditory stimulation. CONCLUSIONS: These changes in waveform by visual and auditory stimulation are thought to be due to the effects of the activation of polymodal neurons, which receive not only somatosensory but also visual and/or auditory inputs, in areas 5 and/or 7 as well as in the medial superior temporal region (MST) and superior temporal sulcus (STS), although a change of attention might also be a factor causing such findings.

Acoustic Stimulation↗

PubMed1999

Autoradiographic evaluation of 99mTc-methylene diphosphonate accumulation in oral cancer invading the mandible.

PURPOSE: Skeletal scintigraphy, a sensitive diagnostic tool used to detect changes in bone, is helpful for evaluating bone invasion by oral cancer. However, the exact sites of accumulation of 99mTc-phosphate compounds in the mandible have not yet been fully elucidated. The aim of this study was to determine the localization of 99mTc-methylene diphosphonate (MDP) in the areas of mandible that have been invaded by cancer. PATIENTS AND METHODS: Seven patients with oral cancer (lower gingiva, 4; tongue, 2; floor of the mouth, 1) who underwent surgical treatment with mandibular bone resection were included in the study. Autoradiography and contact macroradiography were used for evaluation of 99mTc-MDP accumulation. RESULTS: Radioactivity reflecting accumulation of 99mTc-MDP was documented encircling the portion of the mandible with cancerous invasion, suggesting that 99mTc-MDP accumulated in immature bone. High uptake also was found in the periosteal reactive bone around the cortical bone. CONCLUSIONS: The amount of increased 99mTc-MDP circumscribing carcinoma invasion varies among cases. Additionally, uptake may not correspond directly with the amount of the carcinoma invasion; that seen in periosteal bone could be attributed mistakenly to bone invasion in planar scintigraphy.

Aged↗

PubMed1999

Intra-striatal phencyclidine inhibits N-methyl-D-aspartic acid-stimulated increase in glutamate levels of freely moving rats.

1. The authors investigated the effect of local phencyclidine (phenylcyclohexylpiperidine, PCP) on extracellular levels of glutamate and gamma-amino butyric acid (GABA) in rat striatum using in vivo microdialysis. 2. Intrastriatal infusion of PCP (1 mM) via a microdialysis probe did not alter the basal extracellular levels of either glutamate or GABA. Addition of N-methyl-D-aspartic acid (NMDA; 0.2, 0.5 and 1 mM) to the perfusion medium resulted in a dose-dependent increase in extracellular levels of glutamate. 3. Intrastriatal infusion of tetrodotoxin (0.1, 1, 10 microM), a highly selective blocker of voltage-dependent sodium channels, significantly attenuated the NMDA-stimulated release of glutamate, suggesting that NMDA-evoked release of glutamate originated from the neuronal pool and that the increase of striatal glutamate level was regulated indirectly via NMDA receptors. 4. The NMDA-induced release of glutamate was reduced significantly by pretreatment with local PCP (1 mM). Dizocilpine (MK801; 0.2 mM), a non-competitive NMDA antagonist, completely inhibited the NMDA-stimulated release of glutamate. 5. These results suggest that, in the striatum, PCP inhibits corticostriatal glutamatergic neurotransmission by inhibiting the release of glutamate probably via postsynaptic NMDA receptors.

Animals↗

PubMed1999

Echogenicity of fetal lung and liver quantified by the grey-level histogram width.

Grey-level histogram width (GLHW) values of fetal lung and liver were studied in 52 healthy fetuses in 24 to 38 weeks of pregnancy, comparing them to the mean grey level (MGL), grey-level standard deviation (GLSD) and the coefficient of variation (GLCV). Fetal lung GLHW was larger in 30-38 weeks than at 24-29 weeks, but there was no change in liver GLHW. GLHW was smaller in fetal lung than in the liver in 24-29 weeks, with no difference in 30-38 weeks. The lung/liver GLHW ratios were less than 1 in 24-29 weeks, but they were 1 or more in 30-35 weeks. Both MGL of fetal lung and liver showed linear increases during pregnancy, but no difference was found between the two. Fetal lung GLSD tended to decrease during pregnancy. The GLCV values of fetal lung and liver decreased during pregnancy, and differed between 24-29 weeks and 30-38 weeks, whereas there was no difference between fetal lung and liver. The correlation coefficients of GLHW and MGL of fetal lung and liver to the weeks of pregnancy were moderate, and the coefficients of GLSD and GLCV to the weeks of pregnancy were small. In conclusion, quantitatively measured echogenicity of fetal lung increased in 30 or more weeks of pregnancy, and suggested antepartum changes of fetal lung tissue. The GLHW is reliable, because it was reproducible in various gain settings of various ultrasonic imaging devices. The MGL, GLSD and GLCV are less reliable, because the grey level varied by the gain changes among various machines.

Embryonic and Fetal Development↗

PubMed1999

Relationship between endothelin-1 extraction in the peripheral circulation and systemic vascular resistance in patients with severe congestive heart failure.

OBJECTIVES: This study was done to determine the spillover and extraction of endothelin-1 (ET-1) in the peripheral circulation, and to evaluate the factors that regulate local ET-1 extraction in the peripheral circulation in patients with congestive heart failure (CHF). BACKGROUND: The relationship between the spillover and extraction of the ET-1 in the peripheral circulation and systemic vascular resistance (SVR) has not been fully clarified. METHODS: We measured plasma levels of ET-1 both in femoral artery (FA) and femoral vein (FV) in 93 patients with CHF. RESULTS: Plasma ET-1 was significantly higher in FV than in FA in New York Heart Association (NYHA) functional class II patients, but there was no difference of ET-1 between FA and FV in functional class III patients. In patients with functional class IV, plasma ET-1 was significantly lower in FV than in FA, and SVR was significantly higher than in patients with NYHA class II or class III. Moreover, a significant positive correlation existed between plasma ET-1 extraction across the lower leg and SVR in these patients. Among the various neurohumoral factors and hemodynamics, plasma levels of ET-1, angiotensin II in the FA showed an independent and significant relationship with the plasma arteriovenous difference of ET-1 in the lower limb. CONCLUSIONS: Circulating ET-1 is extracted in peripheral circulation in patients with severe CHF, suggesting the possibility of upregulation of ET receptors of vascular beds in the lower limb in these patients. The peripheral extraction of ET-1 correlates with SVR in severe CHF patients and is mainly regulated by the local ET-1 and renin angiotensin systems.

Adolescent↗

PubMed1999

A new quadruple therapy for Helicobacter pylori: influence of resistant strains on treatment outcome.

BACKGROUND: There have been no reports concerning the efficacy and safety of a 1-week quadruple therapy regimen of omeprazole, amoxycillin, roxithromycin and metronidazole for Helicobacter pylori infections and the impact of primary resistance on the eradication rate. METHODS: One hundred and sixty-nine consecutive patients with peptic ulcer disease as well as gastritis with biopsy-proven H. pylori infection were entered into an open study of omeprazole 20 mg o.m., amoxycillin 500 mg t.d.s., roxithromycin 150 mg b.d., and metronidazole 250 mg t.d.s. Helicobacter pylori status was determined by urease test, histology and culture. Susceptibility to amoxycillin, metronidazole and roxithromycin was determined by the E-test. RESULTS: H. pylori was eradicated in 155 out of 169 (92%; 95% CI 88-96%) by intention-to-treat analysis, and in 155 out of 163 (95%; 95% CI 92-98%) by per protocol analysis. The prevalence of primary resistance against amoxycillin, roxithromycin and metronidazole was 2 out of 166 (1%), 16 out of 166 (10%) and 27 out of 166 (16%), respectively. H. pylori was eradicated in 25 out of 27 (93%) patients with metronidazole-resistant strains compared with 130 out of 136 (96%) in patients with metronidazole-sensitive strains of H. pylori. It was eradicated in 15 out of 16 (94%) patients with roxithromycin-resistant strains while in 140 out of 147 (95%) patients with roxithromycin-sensitive strains of H. pylori, and in two out of two (100%) patients with amoxycillin-resistant stains compared with 153 out of 161 (95%) in patients with amoxycillin-sensitive strains. H. pylori was eradicated in three out of four (75%) patients with double resistance against metronidazole and roxithromycin compared with 152 out of 159 (96%) patients with sensitive strains to metronidazole and or roxithromycin. None of these differences were statistically significant. Severe side-effects were found in only one out of 169 patients-anaphylaxis due to penicillin. CONCLUSIONS: The 1-week quadruple therapy with omeprazole, amoxycillin, metronidazole and roxithromycin was found to eradicate H. pylori in over 90% of all patients. This regimen was also found to be beneficial for patients with pre-treatment resistant strains to metronidazole, roxithromycin or amoxycillin, and was observed to be safe and well-tolerated.

Adult↗

PubMed1999

A new member of the alpha4-related molecule (alpha4-b) that binds to the protein phosphatase 2A is expressed selectively in the brain and testis.

A murine alpha4, identified in lymphocytes, binds to protein phosphatase 2A (PP2A). We found another murine alpha4-related gene (named alpha4-b) expressed selectively in the brain and testis. The alpha4-b transcript is expressed in the brain and testis, but is not detected in the spleen, thymus, bone marrow, liver, kidney, lung, heart or muscle. In-situ RNA hybridization analysis suggested that alpha4-b is expressed in most neuronal cells in the brain, but it is not expressed in the glial cells. The alpha4-b cDNA encodes a putative protein that is highly homologous (66% identity in amino-acid sequence) to the alpha4 molecule. The alpha4-b protein associates with the catalytic subunit of PP2A (PP2Ac), suggesting that the alpha4-b protein is involved in the regulation of phosphatase activity in neuronal cells.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Smooth muscle tumors of the esophagus: clinicopathological findings in six patients.

Preoperatively, it is difficult to discriminate leiomyoma and leiomyosarcoma of the esophagus, which are rare smooth muscle tumors. The objective of this study was to evaluate the clinicopathological findings of this unusual lesion. A search of the surgery archives of the Toyama Prefectural Central Hospital of Pathology revealed six cases of esophageal smooth muscle tumors. Clinicopathological findings were reviewed retrospectively. Only three patients (50%) presented with dysphagia, and the remaining three patients were asymptomatic. These patients underwent surgical excision. Histologically four of the six tumors were leiomyomas, and the other two tumors were leiomyosarcomas. Two tumors were in the upper to middle esophagus, and the remaining four were in the distal esophagus. On endoscopic examination, all tumors were noted to be polypoid. The two leiomyosarcomas measured over 5 cm and the four leiomyomas less than 4 cm. Neither ulceration nor necrosis proved to be of use in discriminating leiomyoma and leiomyosarcoma. The two patients with leiomyosarcoma died of liver metastasis 10 and 22 months after the treatment. Patients with leiomyosarcoma presented with distant metastasis and/or recurrence, with hematogeneous metastasis being the predominant type of recurrence.

Adult↗

PubMed1999

Number of lymph node metastases influences survival in patients with thoracic esophageal carcinoma: therapeutic value of radiation treatment for recurrence.

We retrospectively investigated whether the number of involved lymph nodes and the radiation therapy for recurrence affect survival in patients with thoracic esophageal carcinoma. Eighty-nine patients underwent surgical resection and reconstruction for thoracic esophageal squamous cell carcinoma beyond the mucosal layer. Patients were classified into three groups: group 1 comprised 40 patients without lymph node involvement; group 2 comprised 34 patients with 1-3 positive nodes; and group 3 comprised 15 patients with > or = 4 involved lymph nodes. The 3-year and 5-year survival rates were 77.5% and 73.2% respectively in group 1, 64.8% and 55.8% respectively in group 2, and 28.1% and 0% respectively in group 3. The mean survival time (MST) mean +/- SD of the patients in group 3 (772.1 +/- 146.2 days) was significantly shorter than that of patients in group 1 (3728.5 +/- 320.7 days, p < 0.0001) and group 2 (2330.4 +/- 344.3 days, p = 0.0130). The MST of the patients in group 2 was also significantly shorter than that of patients in group 1 (p = 0.0366). Patients with recurrent lymph nodes that were localized were treated effectively with radiation therapy. We conclude that the number of lymph node metastases influences survival in thoracic esophageal cancer. Early detection as well as radiation therapy for recurrent lymph node metastases is effective in improving long-term survival.

Adult↗

PubMed1999

Amyloid beta protein (25-35) phosphorylates MARCKS through tyrosine kinase-activated protein kinase C signaling pathway in microglia.

Myristoylated alanine-rich C kinase substrate (MARCKS) is a widely distributed specific protein kinase C (PKC) substrate and has been implicated in membrane trafficking, cell motility, secretion, cell cycle, and transformation. We found that amyloid beta protein (A beta) (25-35) and A beta (1-40) phosphorylate MARCKS in primary cultured rat microglia. Treatment of microglia with A beta (25-35) at 10 nM or 12-O-tetradecanoylphorbol 13-acetate (1.6 nM) led to phosphorylation of MARCKS, an event inhibited by PKC inhibitors, staurosporine, calphostin C, and chelerythrine. The A beta (25-35)-induced phosphorylation of MARCKS was inhibited by pretreatment with the tyrosine kinase inhibitors genistein and herbimycin A, but not with pertussis toxin. PKC isoforms alpha, delta, and epsilon were identified in microglia by immunocytochemistry and western blots using isoform-specific antibodies. PKC-delta was tyrosine-phosphorylated by the treatment of microglia for 10 min with A beta (25-35) at 10 nM. Other PKC isoforms alpha and epsilon were tyrosine-phosphorylated by A beta (25-35), but only to a small extent. We propose that a tyrosine kinase-activated PKC pathway is involved in the A beta (25-35)-induced phosphorylation of MARCKS in rat microglia.

Amyloid beta-Peptides↗

PubMed1999

Report of the annual statistical survey of the Japanese Society for Dialysis Therapy in 1996.

BACKGROUND: Nearly 170,000 patients were treated by maintenance renal replacement therapy (RRT) in Japan in 1996. The current status of Japanese patients on RRT might, in some way, be suggestive for patients on RRT in other countries. METHODS: The Japanese Society for Dialysis Therapy conducts a questionnaire survey of virtually every dialysis facility in Japan at the end of each year. Here we present the results of our survey of patients undergoing RRT as of the end of 1996, as well as five-year trends (1992-1996) in some of the data. RESULTS: The response rate was 99.8%. At the end of 1996, there were 167,192 patients on maintenance RRT in Japan (1,328 persons per million population). The numbers of patients on maintenance RRT continued to increase during the five-year period. The gross mortality rate for that period ranged from 9.4% to 9.7%. Cuprammonium rayon was the most commonly used material (24.0%) for dialyzer membranes, followed by cellulose triacetate (18.7%). Approximately 5.0% of hemodialysis (HD) patients had a prior history of surgical release of carpal tunnel. The longer the years on HD therapy, the greater the proportion of patients with a history of such an operation. The predialysis plasma beta 2-microglobulin concentration was highest in patients aged 30 to 45 years and declined slightly after the age of 45. There was no significant difference in the HbA1c level between continuous ambulatory peritoneal dialysis and HD patients, both in whom diabetes was the disease causing renal failure. Moreover, among HD patients with diabetes, there was a clear tendency for the HbA1c level to be higher when the normalized protein catabolic rate was higher. CONCLUSION: This report summarizes the latest results of the survey on Japanese patients on RRT.

Adult↗

PubMed1999

Plasma brain natriuretic peptide level as a biochemical marker of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction. Comparison with plasma angiotensin II and endothelin-1.

AIMS: To evaluate the level of plasma brain natriuretic peptide as a predictor of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction. METHODS: We measured plasma levels of atrial natriuretic peptide, brain natriuretic peptide, norepinephrine, angiotensin II, and endothelin-1 and monitored haemodynamic parameters in 290 consecutive patients with asymptomatic or minimally and newly symptomatic left ventricular dysfunction (functional classes I-II, mean left ventricular ejection fraction=37%). All patients were followed up for a median period of 812 days. The Cox proportional hazards model was used to assess the association of variables with mortality and morbidity. RESULTS: At the end of the follow-up, 24 patients had suffered cardiac death and 25 had been hospitalized for worsening heart failure during the follow-up period. Among 21 variables such as clinical characteristics, treatment, haemodynamics, and neurohumoral factors, high levels of plasma brain natriuretic peptide (P<0.0001), norepinephrine (P=0.042), left ventricular end-diastolic volume index (P=0.0035), and left ventricular end-diastolic pressure (P=0.033) were shown to be independent predictors of mortality and morbidity by stepwise multivariate analysis. Moreover, only a high level of plasma brain natriuretic peptide (P<0.0001) was shown to be an independent predictor of mortality in these patients. CONCLUSIONS: These results indicate that a high plasma brain natriuretic peptide level provides information about mortality and morbidity in patients with asymptomatic or minimally symptomatic left ventricular dysfunction.

Adolescent↗

PubMed1999

Larger anastomoses in angiotensinogen-knockout mice attenuate early metabolic disturbances after middle cerebral artery occlusion.

Abnormalities in the homeostasis of the renin-angiotensin system have been implicated in the pathogenesis of vascular disorders, including stroke. The authors investigated whether angiotensinogen (AGN) knockout mice exhibit differences in brain susceptibility to focal ischemia, and whether such differences can be related to special features of the collateral circulation. Wild-type and AGN-knockout mice were submitted to permanent suture occlusion of the middle cerebral artery (MCA). The collateral vascular system was visualized by systemic latex infusion, and the ischemic lesions were identified by cresyl-violet staining. The core and penumbra of the evolving infarct were differentiated by bioluminescence and autoradiographic imaging of ATP and protein biosynthesis, respectively. In wild-type mice, mean arterial blood pressure was 95.0 +/- 8.6 mm Hg, and the diameter of fully relaxed anastomotic vessels between the peripheral branches of the anterior and middle cerebral arteries 26.6 +/- 4.0 microm. In AGN knockouts, mean arterial blood pressure was significantly lower, 71.5 +/- 8.5 mm Hg (P < .01), and the anastomotic vessels were significantly larger, 29.4 +/- 4.6 microm (P < .01). One hour after MCA occlusion, AGN-knockout mice exhibited a smaller ischemic core (defined as the region of ATP depletion) but a larger penumbra (the area of disturbed protein synthesis with preserved ATP). At 24 hours after MCA occlusion, this difference disappeared, and histologically visible lesions were of similar size in both strains. The observations show that in AGN-knockout mice the more efficient collateral blood supply delays ischemic injury despite the lower blood pressure. Pharmacologic suppression of angiotensin formation may prolong the therapeutic window for treatment of infarcts.

Acute Disease↗

PubMed1999

Pharmacologic characterization of FR172516: a new combined calcium channel-blocking and beta-adrenoceptor-blocking agent.

The pharmacologic characterization of FR172516, a new combined calcium channel-blocking and beta-adrenoceptor-blocking agent, was studied and compared with amlodipine in receptor-binding assay and in vivo studies. In the binding assay, Ki values of FR172516 for calcium channel and beta-receptor were 29.3 nM and 44.1 nM, respectively. In the in vivo studies with pithed rats, FR172516 shifted the dose-response curves of isoproterenol in heart rate to the right, suggesting that this compound has a antiadrenoceptor effect in vivo. The hypotensive effect of FR172516, which could be mainly attributed to its calcium channel-blocking action, was compared with that of amlodipine in normotensive Wistar rats (NTRs), spontaneously hypertensive rats (SHRs), and renal hypertensive dogs (RHDs). FR172516 showed more potent hypotensive action than amlodipine when administered intravenously to NTRs, and apparent bradycardia was seen only with FR172516. In SHRs, FR172516 showed a long-lasting hypotensive action and dose-dependently decreased heart rate, whereas amlodipine scarcely affected heart rate. In RHDs, oral administration of FR172516 once daily for 5 days decreased blood pressure without reflex tachycardia or an increase of plasma renin activity. On the other hand, amlodipine, in the dose at which hypotensive effects equipotent to those of FR172516 were observed, produced apparent reflex tachycardia and concomitant increase of plasma renin. These results indicate that FR172516 has a potent long-lasting antihypertensive effect without activating sympathetic tone by calcium channel-blocking and beta-adrenoceptor-blocking actions.

Adrenergic beta-Antagonists↗