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Biomedical subjects

I Abe

Publications and source records attributed to I Abe.

At least 127 records · Page 7Linked to original sources
PubMed1997

[Evaluation by specialists of the Guidelines on Treatment of Hypertension in the Elderly--the second questionnaire survey].

The Guidelines on Treatment of Hypertension in the Elderly, 1995 was published by the Research Group for Guidelines on Treatment of Hypertension in the Elderly Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare. To assess the guidelines, and to further investigate the changes in the therapeutic policy for hypertension in the elderly, we mailed a questionnaire to 133 Japanese hypertension specialists who had replied to the first mailed questionnaire in 1993. We received 102 replies (77%). Overall, the guidelines were scored 4.3/5.0. More than 95% of the specialists agreed with levels of blood pressure (BP) indicative for treatment, as well as the goal of BP control. The guidelines propose that the rate of increase of the drug dose should be very slow, at least every four weeks, and that the target BP be reached after two months. The majority of the specialists agreed with this. However, 10% of them preferred to follow patients every two weeks. The guidelines propose long-acting Ca antagonists and ACE inhibitors as the first choice of drug for the treatment of uncomplicated hypertension in the elderly. Two-thirds of the specialists agreed. However, 17% of specialists proposed adding diuretics or beta-blockers to the first line therapy. Ten specialists (10%) expressed concerns about Ca antagonists and three (3%) insisted on withdrowing them from the first line of drugs. In the guidelines, alpha and beta blockers are designated as relatively contraindicated in elderly patients with hypertension, but half the specialists answered that these drugs can be used safely in elderly patients. These findings indicate that the therapeutic policy of Japanese specialists in hypertension in the elderly has not changed substantially for three years.

Aged↗
PubMed1997

Enhanced electrical activity in mesenteric arteries from salt-loaded Dahl salt-sensitive rats: actions of prostaglandin H2 on membrane channels.

Salt loading increases blood pressure in Dahl salt-sensitive (Dahl S) rats. We have previously shown that the mesenteric artery of salt-loaded Dahl S rats exhibits enhanced electrical activity that is corrected by a cycloxygenase inhibitor, indomethacin. Prostaglandin H2 (PGH2) is a product of cycloxygenase that is known as an intrinsic vasoconstricting factor in spontaneously hypertensive rats. Our hypothesis is that tissue production of PGH2 would be involved in the enhanced electrical activity of arteries from salt-loaded Dahl S rats. In the present study, to clarify this possibility, we evaluated the actions of PGH2 on membrane channels in arterial cells from Dahl S rats. Membrane currents were recorded by whole-cell voltage clamp technique in single smooth muscle cells from the mesenteric artery. Application of PGH2 evoked an inward current that was mainly dependent on extracellular Na+ in the physiological extracellular solution. When high Ba2+ solution was used for the extracellular solution, PGH2 also evoked the inward current, suggesting that a divalent cation, such as Ba2+ or Ca2+, could permeate the PGH2-activated channels. In contrast, the L-type Ca2+ channel currents were not enhanced by the application of PGH2. The present results suggest that production of PGH2 contributes to the enhanced electrical activity by activating cation-permeable channels and depolarizing the membrane potential. PGH2 also directly stimulates the Ca2+ influx by activating Ca2+ permeable channels.

Animals↗
PubMed1997

[Geometrical distribution of newly formed blood vessels in diabetic retinopathy].

Outbreak sites of newly formed blood vessels (NFVs) in proliferative diabetic retinopathy (PDR) were analyzed geometrically. A montage was made of fluorescein fundus angiography photographs of 109 eyes and applied to a two dimensional x-y plane in which the center of the optic disc was taken as the origin. Thus each NFV acquired a coordinate value (x, y). After a coordinate transformation of this x-y plane designed to correct the parafoveal distortion of vascular distribution, a polar coordinate value (r, theta) of the NFV was calculated. The frequencies of NFVs were analyzed statistically relating to both theta, which is the angle around the origin, and r, which is the distance from the origin. The average theta was 2.74 +/- 1.72 (mean +/- standard deviation) radians and the outbreak frequency of NFVs showed a homogeneous distribution which was not influenced by any difference in theta. As for r, the frequency corrected as a truncated distribution at r = 0 showed a normal distribution with an average of 1.45 +/- 0.8. The outbreak of NFVs in PDR is a phenomenon in which accidental elements are strongly concerned and it is thought to be difficult to predict the site at early stage of retinopathy.

Adult↗
PubMed1996

Peroxidase-catalyzed generation of catechin oligomers that inhibit glucosyltransferase from Streptococcus sobrinus.

Oolong tea extract (OTE) and the purified polymeric polyphenols from OTE have been found to inhibit glucosyltransferase (GTase) of mutans streptococci. In view of the partial fermentation characteristic of oolong tea, we describe here an in vitro model reaction system to produce partially fermented products of D-(+)-catechin or green tea extract (GTE) using horseradish peroxidase. A dimeric catechin molecule was identified as dehydro-dicatechin A by instrumental analyses. The molecular size of some oligomeric catechins was estimated by the elution profile with HPLC. These catechin oligomers markedly inhibited GTase from Streptococcus sobrinus 6715. As the degree of polymerization of catechin or GTE increased, GTase was inhibited more effectively. These results suggest that polymeric polyphenols found in OTE are synthesized by partial fermentation due to oxidases/peroxidases present in tea leaves.

Bacterial Adhesion↗
PubMed1996

Circadian variations of blood pressure in patients with sequelae of carbon monoxide poisoning.

It has been shown that carbon monoxide poisoning causes necrosis of the globus pallidum and the cerebral cortex, and a diffuse demyelination of the cerebral subcortical white matter, resulting in the impairment of the higher brain functions manifested as memory disturbances, apraxia, and agnosia. The purpose of the present study was to determine the effects of the lesions in the brain caused by carbon monoxide poisoning on the circadian changes in blood pressure and pulse rate. We measured the ambulatory blood pressure in 15 male patients with the sequelae of acute carbon monoxide poisoning and 16 age- and sex-matched controls. Using either brain computed tomography or brain magnetic resonance imaging, we determined that seven patients had lesions in the globus pallidum bilaterally, four had lesions in the parietotemporooccipital lobe bilaterally, and five had multiple deep white matter lesions. Circadian variations of blood pressure and pulse rate did not show any significant differences in either group. The average 24-h blood pressures were 120.8 +/- 2.2 (systolic)/74.1 +/- 1.5 mm Hg (diastolic) in the patients and 117.4 +/- 2.7/74.5 +/- 2.1 mm Hg in the controls. The daytime (6:00 to 21:00) and nighttime (21:00 to 6:00) blood pressures were 127.3 +/- 2.3/78.0 +/- 1.5 mm Hg and 109.7 +/- 2.4/67.4 +/- 1.7 mm Hg in the patients, and 121.6 +/- 2.9/77.5 +/- 2.2 mm Hg and 110.0 +/- 2.7/69.3 +/- 1.8 mm Hg in the controls, respectively. Furthermore, there were no differences in cardiovascular and plasma catecholamine responses induced by either a head-up tilt or a cold pressor test between the two groups. It is concluded that diffuse or multiple lesions in bilateral cerebral hemispheres caused by carbon monoxide poisoning per se do not affect the circadian changes in blood pressure and pulse rate observed in normotensive subjects.

Aged↗
PubMed1996

Circadian blood pressure in patients in a persistent vegetative state.

We examined circadian variations in blood pressure, pulse rate, and other physiological variables, including hormone levels, in 16 patients in a persistent vegetative state (mean age -/+ SE; 66.1 -+/ 3.9 yr). Cerebrovascular accident was responsible for brain damage in 12 (75%) of the 16 patients. Blood pressure was measured for 24 h with an ambulatory blood pressure monitoring device. We monitored the temperature of the urinary bladder and measured urinary excretion of epinephrine, norepinephrine, 17-hydroxycorticosteroids, water, and sodium. When data were analyzed by analysis of variance, significant circadian changes were observed in body temperature and urinary excretion of hormones and sodium, but not in blood pressure or pulse rate. Individual analysis of rhythmicity using the cosinor method detected small but significant circadian variations in blood pressure and pulse rate in five of six patients who showed a simple organized response to noxious external stimuli. The disappearance of variation in blood pressure in patients in a vegetative state appeared to be related, in part, to the lack of response to external stimuli. Our findings suggest that the circadian variation in blood pressure may largely depend on external environmental factors.

Adult↗
PubMed1996

Hyperinsulinemia and left ventricular geometry in a work-site population in Japan.

The present study was designed to test whether hyperglycemia or hyperinsulinemia influences left ventricular mass and geometry. An echocardiogram and 75-g oral glucose tolerance test were performed in 210 normotensive and 180 mildly to moderately hypertensive male workers in a bus company who were free from cardiac diseases and were not taking medication for hypertension and diabetes mellitus. When we divided subjects into four groups according to the left ventricular geometric pattern using left ventricular mass index of 110 g/m2 and relative wall thickness (ratio of 2 x posterior wall thickness to end-diastolic left ventricular diameter) of 0.44, body mass index and systolic blood pressure were higher in those with concentric hypertrophy and eccentric hypertrophy. In addition, hemoglobin A(Ic) level and the sum of fasting and 2-hour postload serum glucose levels were higher in subjects with concentric hypertrophy. In subjects without diabetes mellitus (n=336), 2-hour postload serum insulin level and the sum of fasting and 2-hour postload serum insulin levels tended to be higher in those with concentric hypertrophy and concentric remodeling. In multiple regression analysis, the sum of glucose levels (or hemoglobin A(Ic) level) in all subjects and the sum of insulin (or 2-hour postload insulin) levels in subjects without diabetes mellitus significantly correlated with relative wall thickness, independent of age, systolic blood pressure, and body mass index. Neither glucose nor insulin levels correlated with left ventricular mass index. Our results suggest that hyperglycemia and hyperinsulinemia may promote concentric changes in the left ventricle in normotensive and mildly to moderately hypertensive men.

Adult↗
PubMed1996

Impaired action of levcromakalim on ATP-sensitive K+ channels in mesenteric artery cells from spontaneously hypertensive rats.

The purpose of the present study was to test the hypothesis that properties of ATP-sensitive K+ channels are altered in arterial smooth muscle cells of hypertensive rats. Using a patch-clamp technique, we compared effects of a K+ channel opener, levromakalim, on membrane currents in mesenteric artery cells from adult Wistar Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR) treated or not treated with hydralazine. Blood pressure was significantly higher in SHR than in WKY or hydralazine-treated SHR. Levcromakalim evoked a time-independent and voltage-insensitive current in a dose-dependent manner in the whole-cell clamp configuration. The reversal potential of the evoked current depended on extracellular K+ concentration. Application of 3 micromol/L glibenclamide, a specific blocker of ATP-sensitive K+ channels, abolished the levcromakalim-evoked current; however, the current was unaffected by either 1 mmol/L tetraethylammonium or 0.3 micromol/L charybdotoxin. These results suggest that the levcromakalim-evoked current was carried through ATP-sensitive K+ channels. In SHR cells, the maximal slope conductance of the levcromakalim-evoked current, normalized by cell capacitance, was decreased, and the dose-response curve was shifted to the right compared with WKY cells. The levcromakalim action was not impaired in cells from hydralazine-treated SHR. In conclusion, the action of levcromakalim on ATP-sensitive K+ channels in SHR mesenteric artery muscle cells was impaired compared with WKY cells. This impairment was corrected by long-term antihypertensive treatment.

Animals↗
PubMed1996

Angiotensin II increases norepinephrine turnover in the anteroventral third ventricle of spontaneously hypertensive rats.

We evaluated the effect of angiotensin II (Ang II) administered by intracerebroventricular injection on norepinephrine turnover in the anteroventral third ventricle in adult spontaneously hypertensive rats (SHR, n = 35) and age-matched Wistar-Kyoto rats (WKY, n = 38). Ang II (100 ng) or saline (vehicle control) was administered into the cerebral ventricle 30 minutes after injection of alpha-methyl-p-tyrosine (250 mg/kg IP). Norepinephrine turnover was assessed by evaluation of the norepinephrine concentration before and 1 hour after such administration. The pressor response to Ang II administration was significantly greater in SHR than in WKY (+43 +/- 3 versus +23 +/- 2 mm Hg, P < .01). Baseline norepinephrine turnover (response to saline) was reduced in the ventral median preoptic nucleus of SHR. Ang II significantly increased norepinephrine turnover in the organum vasculosum lamina terminalis and ventral median preoptic nucleus of SHR (organum vasculosum lamina terminalis: 40 +/- 5% by Ang II versus 18 +/- 6% by saline, P < .05; ventral median preoptic nucleus: 32 +/- 3% by Ang II versus 21 +/- 2% by saline, P < .05) but not of WKY (37 +/- 5% versus 29 +/- 5%, P = NS, and 30 +/- 2% versus 32 +/- 3%, P = NS, respectively). Thus, norepinephrine turnover in the anteroventral third ventricle region induced by intracerebroventricular administration of Ang II was increased in SHR. This effect may contribute to the enhanced pressor response to central Ang II seen in this model.

Angiotensin II↗
PubMed1996

Serial changes in blood pressure and neurohormone levels after the onset of lacunar stroke.

To assess serial changes in blood pressure and its circadian variation following a lacunar stroke, the authors studied 7 patients who developed a single lacunar infarction in either the internal capsule or the corona radiata. Blood pressure and pulse rate were monitored noninvasively for twenty-four hours by an ambulatory blood pressure monitoring device in the acute, subacute, and chronic phases of the strokes. In the acute and chronic phases, the authors also measured urinary excretion of catecholamines every 6 hr, and serum cortisol concentration at 9:00, 17:00, and 21:00 hr. The patients were free from antihypertensive agents during the study. The twenty-four-hour averages of both systolic and diastolic blood pressure in the chronic phase were lower than those in the acute phase (P < 0.05). A nighttime fall in blood pressure was observed in the subacute and chronic phases (P < 0.05), but not in the acute phase. Urinary excretion of epinephrine at night in the acute phase was significantly higher than that in the chronic phase (P < 0.05). Serum levels of cortisol at 17:00 and 21:00 hr in the acute phase also exceeded those in the chronic phase (P < 0.05 and P < 0.01, respectively). The authors conclude that an increased secretion of epinephrine and cortisol might, at least in part, contribute to a high blood pressure and a lack of circadian variation in blood pressure in the acute phase of lacunar stroke.

Acute Disease↗
PubMed1996

Insulin and cardiovascular diseases in Japanese work-site population with borderline to mild hypertension.

To clarify whether significant interrelations between hyperinsulinemia and cardiovascular diseases exist in Japanese, we analyzed serum insulin levels, fasting and after oral glucose load, in relation to blood pressure (BP), serum lipids, and incidence of acute myocardial infarction (MI) and stroke in 584 male employees of a railroad company with borderline to mild hypertension (age: 49 +/- 7 years, BP: 139 +/-13/90 +/- 8 mmHg, body mass index: BMI 24.0 +/- 2.8, mean +/- SD). Those who were taking antihypertensive drugs and/or hypoglycemic agents were excluded. The subjects were classified into five groups of comparable size according to sigma IRI (area composed by insulin levels at 0, 1, 2 hours post glucose load). Although averaged age, levels of fasting glucose and HbA1c were not significantly different among quintiles, the hyperinsulinemic groups had higher levels of fasting IRI and sigma glucose. Multiple regression analysis revealed that sigma IRI was associated positively with BMI, sigma glucose, systolic BP, total cholesterol, and negatively with HDL-cholesterol. During 7-year follow-up 7 cases with MI and 15 cases with stroke were registered. The subjects with MI, but not with stroke were involved in higher deciles of insulin levels. These results indicate that the insulin resistance syndrome exists in Japanese middle-aged men with borderline to mild hypertension. The association with cardiovascular morbid events appeared to be evident in coronary heart disease but not in cerebrovascular disease.

Adult↗
PubMed1996

[Guidelines on treatment of hypertension in the elderly, 1995--a tentative plan for comprehensive research projects on aging and health-- Members of the Research Group for "Guidelines on Treatment of Hypertension in the Elderly", Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare of Japan].

We propose the following guidelines for treatment of hypertension in the elderly. 1. Indications for Treatment. 1) Age: Lifestyle modification is recommended for patients aged 85 years and older. Antihypertensive therapy should be limited to patients in whom the merit of the treatment is obvious. 2) Blood pressure: Systolic BP > 160 mmHg, diastolic BP > 90 approximately 10 mmHg. Systolic BP < age + 100 mmHg for those aged 70 years and older. Patients with mild hypertension (140-160/ 90-95 mmHg) associated with cardiovascular disease should be considered for antihypertensive drug therapy. 2. Goal of Therapy for BP: The goal BP in elderly patients is higher than that in younger patients (BP reduction of 10-20 mmHg for systolic BP and 5-10 mmHg for diastolic BP). In general, 140-160/< 90 mmHg is recommended as the goal. However, lowering the BP below 150/85 should be done with caution. 3. Rate of Lowering BP: Start with half the usual dose, observe at the same dose for at least four weeks, and reach the target BP over two months. Increasing the dose of antihypertensive drugs should be done very slowly. 4. Lifestyle Modification: 1) Dietary modification: (1) Reduction of sodium intake is highly effective in elderly patients due to their high salt-sensitivity. NaCl intake of less than 10 g/day is recommended. Serum Na+ should be occasionally measured. (2) Potassium supplementation is recommended, but with caution in patients with renal insufficiency. (3) Sufficient intake of calcium and magnesium is recommended. (4) Reduce saturated fatty acids. Intake of fish is recommended. (2) Regular physical activity: Recommended exercise for patients aged 60 years and older: peak heart rate 110/minute, for 30-40 minutes a day, 3-5 days a week. (3) Weight reduction. (4) Moderation of alcohol intake, smoking cessation. 5. Pharmacologic Treatment: 1) Initial drug therapy. First choice: Long-acting (once or twice a day) Ca antagonists or ACE inhibitors. Second choice: Thiazide diuretics (combined with potassium-sparing diuretic). 2) Combination therapy. (1) For patients without complications, either of the following is recommended. i) Ca antagoinst + ACE inhibitor, ii) ACE inhibitor + Ca antagonist (or low-dose diuretics), iii) diuretic + Ca antagonist (or ACE inhibitor), iv) beta-blockers, alpha 1-blockers, alpha + beta blockers can be used according to the patho-physiological state of the patient. (2) For patients with complications. Drug(s) should be selected according to each complication. 3) Relatively contraindicated drugs. beta-Blockers and alpha 1-blockers are relatively contraindicated in elderly patients with hypertension in Japan. Centrally acting agents such as reserpine, methyldopa and clonidine are also relatively contraindicated beta-Blockers are contraindicated in patients with congestive heart failure, arteriosclerosis obliterans, chronic obstructive pulmonary disease, diabetes mellitus (or glucose intolerance), or bradycardia. These conditions are often present in elderly subjects. Elderly subjects are susceptible to alpha 1-blocker-induced orthostatic hypotension, since their baroreceptor reflex is diminished. Orthostatic hypotension may cause falls and bone fractures in the elderly.

Aged↗
PubMed1995

Molecular cloning, characterization, and functional expression of rat oxidosqualene cyclase cDNA.

A cDNA encoding rat oxidosqualene lanosterol-cyclase [lanosterol synthase; (S)-2,3-epoxysqualene mutase (cyclizing, lanosterol-forming), EC 5.4.99.7] was cloned and sequenced by a combination of PCR amplification, using primers based on internal amino acid sequence of the purified enzyme, and cDNA library screening by oligonucleotide hybridization. An open reading frame of 2199 bp encodes a M(r) 83,321 protein with 733 amino acids. The deduced amino acid sequence of the rat enzyme showed significant homology to the known oxidosqualene cyclases (OSCs) from yeast and plant (39-44% identity) and still retained 17-26% identity to two bacterial squalene cyclases (EC 5.4.99.-). Like other cyclases, the rat enzyme is rich in aromatic amino acids and contains five so-called QW motifs, highly conserved regions with a repetitive beta-strand turn motif. The binding site sequence for the 29-methylidene-2,3-oxidosqualene (29-MOS), a mechanism-based irreversible inhibitor specific for the vertebrate cyclase, is well-conserved in all known OSCs. The hydropathy plot revealed a rather hydrophilic N-terminal region and the absence of a hydrophobic signal peptide. Unexpectedly, this microsomal membrane-associated enzyme showed no clearly delineated transmembrane domain. A full-length cDNA was constructed and subcloned into a pYEUra3 plasmid, selected in Escherichia coli cells, and used to transform the OSC-deficient uracil-auxotrophic SGL9 strain of Saccharomyces cerevisiae. The recombinant rat OSC expressed was efficiently labeled by the mechanism-based inhibitor [3H]29-MOS.

Amino Acid Sequence↗
PubMed1995

Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey.

The prevalence of fatty liver in children is unknown and its relationship to obesity is poorly defined. The present study of 810 northern Japanese children (4-12 years old) determined the prevalence of fatty liver in the pediatric population and its relationship to obesity. Diagnosis of fatty liver was based on established real-time ultrasonographic criteria. The overall prevalence of fatty liver was 2.6% and was higher for boys (3.4%) than for girls (1.8%), although not statistically significant (P = 0.15). Fatty liver was found in children as young as 6 years of age. There was no significant association between the prevalence of fatty liver and height (physical growth). There was a strong positive correlation between fatty liver prevalence and established obesity indices: Rohrer's Index--chi 2 linear trend = 59.2, P < 0.0001; body mass index--chi 2 linear trend = 91.6, P < 0.0001; and age-gender-adjusted Japanese standard index of weight for height--chi 2 linear trend = 93.2, P < 0.0001. However, direct measurement of abdominal subcutaneous fat thickness by ultrasonography was the best predictor of fatty liver: chi 2 linear trend = 159, P < 0.0001. These results indicate that fatty liver may develop very early in life, and there is a direct relationship between degree of obesity and fatty liver in children.

Body Height↗
PubMed1995

Identification of the active site of vertebrate oxidosqualene cyclase.

Active site mapping of rat liver oxidosqualene cyclase (OSC), a 78 kDa membrane-bound enzyme, was carried out using the mechanism-based irreversible inhibitor, [3H]29-methylidene-2,3-oxidosqualene. The amino acid sequence of the radiolabeled CNBr peptide fragment showed unexpectedly high similarity to the yeast OSC, plant OSC, and bacterial squalene cyclases. Further, radio analysis established that the two adjacent Asp residues in the highly conserved region (Asp-Asp-Thr-Ala-Glu-Ala, or DDTAEA) were equally labeled by the irreversible inhibitor. This result provided the first information on the structural details of the active site of OSC, and showed for the first time the ancient lineage of this vertebrate enzyme to ancestral eukaryotic and prokaryotic cyclases. Interestingly, the covalently-modified DDXX(D/E) sequence of rat liver OSC showed surprising similarity to the putative allylic diphosphate binding site sequence of other terpene cyclases and prenyl transferases. The Asp-rich motif may act as a point charge to stabilize incipient cationic charge.

Amino Acid Sequence↗
PubMed1995

Disparate circadian variations of blood pressure and body temperature in bedridden elderly patients with cerebral atrophy.

Twenty bedridden elderly patients with normal sleep-wake cycles were studied to evaluate the circadian variations of blood pressure, pulse rate, body core temperature, cortisol, and catecholamines with a focus on their relation to cerebral atrophy. Twenty-four-hour blood pressure (BP) and pulse rate monitorings were done with simultaneous measurement of urinary bladder temperature. Urine was also collected every 4 h to measure 17-hydroxycorticosterone and catecholamines. Based on the brain CT, frontal horn index (FHI: maximal distance between bilateral frontal horns/the corresponding width of the skull) was calculated as an index of cerebral atrophy. Analysis by the cosinor method revealed that the significant circadian rhythm with nocturnal decline was observed in only 9 patients (45%) for BP and in 13 patients (65%) for pulse rate. In contrast, 19 of 20 patients (95%) showed significant circadian rhythms of bladder temperature, with the nadirs appearing between 00:06 and 06:54. In the subgroup of mild cerebral atrophy (FHI < 0.30, n = 11), BP and pulse rate fell modestly but significantly during nighttime, whereas they did not fall in the subgroup of moderate to severe cerebral atrophy (FHI > or = 0.30, n = 9). The possibility could not be excluded that the sleep disturbance might result in the relatively high BP during nighttime. Bladder temperature, 17-hydroxycorticosteroids, and catecholamines showed significant nocturnal falls in both groups. In conclusion, nocturnal fall of BP disappeared in the bedridden elderly patients with cerebral atrophy, which cannot be explained by the change in the circadian variation of the sympathetic nervous system, cortisol, or body core temperature.

Aged↗
PubMed1995

Inhibitory action of betaxolol, a beta 1-selective adrenoceptor antagonist, on voltage-dependent calcium channels in guinea-pig artery and vein.

1. The effects of betaxolol, (+/-)-1-[4-[2-(cyclopropylmethoxy) ethyl] phenoxy]-3-(isopropylamino)-2-propanol hydrochloride, a beta 1-selective adrenoceptor antagonist, on voltage-dependent Ca2+ channels were investigated in single smooth muscle cells from guinea-pig mesenteric artery and portal vein using a whole-cell variant of the patch-clamp technique. Ca2+ channel currents were recorded with bath solutions contained 10 mM Ba2+ for arterial cells and 2 mM Ca2+ for venous cells. 2. Betaxolol inhibited Ca2+ channel currents dose-dependently in both mesenteric artery cells and portal vein cells. The two isomers, (+)-betaxolol and (-)-betaxolol (relative beta-antagonistic efficacies of 0.1 and 1, respectively), had similar potencies for inhibiting Ca2+ channel currents in portal vein cells. Propranolol did not inhibit the currents. Thus the inhibitory action of betaxolol on Ca2+ channel currents was independent of the beta-adrenoceptor. 3. The inhibitory action of betaxolol on Ca2+ channel currents was compared with that of diltiazem and of nifedipine in mesenteric artery cells. The current inhibition depended on the stimulation frequency with all drugs (use-dependent block). All drugs also accelerated the current decay and shifted the voltage-dependent inactivation curve in a negative direction. 4. In conclusion, betaxolol inhibited Ca2+ channel currents in vascular smooth muscle cells. The mode of inhibitory action was similar to that of diltiazem and nifedipine. Our results suggest that betaxolol is a unique beta-adrenoceptor antagonist that has a direct inhibitory action on voltage-dependent Ca2+ channels in vascular smooth muscle cells.

Animals↗