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Biomedical subjects

S Yagi

Publications and source records attributed to S Yagi.

At least 253 records · Page 14Linked to original sources

Relationship between force and Ca2+ concentration in smooth muscle as revealed by measurements on single cells.

The role of Ca2+ in regulating smooth muscle contraction was investigated by measuring isometric force and [Ca2+] simultaneously in individual single smooth-muscle cells. [Ca2+] was measured with fura-2 and a high time-resolution dual-wavelength digital microfluorimeter, and force was measured with an ultrasensitive force transducer attached to a probe around which was tied one end of the cell. Both [Ca2+] and force increase after maximal electrical stimulus, with [Ca2+] increasing considerably before the first detectable increase in force. Force development exhibited maximal sensitivity to [Ca2+] between 150 and 500 nM Ca2+. This Ca2+ sensitivity can account for the fact that many physiological stimuli produce full contraction even though such stimuli only increase Ca2+ to 600-800 nM. When Ca2+ was induced to increase rapidly, the relation between [Ca2+] and force exhibited hysteresis. During the onset of contraction, force at a given [Ca2+] was lower than during the muscle's return to rest, thus suggesting the existence of a slow step(s) linking Ca2+ and force development in smooth muscle. The direction of this hysteresis reversed during contractions in which Ca2+ increased slowly, suggesting that the contractile process becomes desensitized to [Ca2+] with time. These relations between calcium and force in intact single smooth-muscle cells differ in many respects from the relation found previously in chemically permeabilized multicellular preparations of smooth muscle.

Animals↗

Supplemental fosfomycin and/or steroids that reduce cisplatin-induced nephrotoxicity.

The protective effects of fosfomycin and steroids on the nephrotoxicity induced by cisplatin in lung cancer patients were studied by measuring N-acetyl-beta-D-glucosaminidase (NAG) activity in 24-hour urine, creatinine clearance, serum creatinine and blood urea nitrogen as factors of nephrotoxicity. In control patients treated with anticancer drugs containing cisplatin but no supplemental fosfomycin or steroids, the 24-hour urine NAG level increased two-fold (15.5 +/- 7.5, p less than 0.01) over the pretreatment level (8.0 +/- 5.2) 3 days after anticancer therapy. Supplemental fosfomycin or steroids inhibited an increase in urinary NAG level 3 days after the anticancer therapy. There were, however, no significant changes in creatinine clearance, serum creatinine and blood urea nitrogen levels before and after anticancer and/or supplemental therapies. These results suggest the possibility that supplemental treatment with fosfomycin, like that with steroids, reduces cisplatin-induced nephrotoxicity, especially proximal tubular damage.

Acetylglucosaminidase↗

Alterations to the vascular vasodepressor prostaglandin system in DOCA-salt hypertensive rats and their enzymatic analysis.

To define the roles of vascular prostacyclin (PGI2) synthase for PGI2 generation in deoxycorticosterone acetate (DOCA)-salt hypertension, we investigated PGI2 synthase, phospholipase A2 and phospholipase C activities in the aortic wall of DOCA-salt prehypertensive and established hypertensive rats. Vascular PGI2 generation in the DOCA-salt hypertensive rats was increased by 91%, and was associated with an 88% increase in PGI2 synthase activity and lowered phospholipase C and A2 activity. In the prehypertensive stage, DOCA-salt rats showed reduced vascular PGI2 generation. Prostacyclin synthase activity was equal to that of controls. These data clearly suggest that DOCA-salt hypertensive rats increase their vascular PGI2 generation when they develop hypertension, and that this may be due to the activation of vascular PGI2 synthase.

Animals↗

Renal nerve and cardiovascular responses to cardiac receptor stimulation in rabbits.

It has been shown that a species difference exists among cats, dogs, and monkeys in the reflex response to cardiac sympathetic afferent stimulation with bradykinin (BK). This study was performed to determine the arterial blood pressure (ABP), heart rate (HR), and renal nerve activity (RNA) responses to epicardial BK applications in the intact and sinoaortic-denervated and vagotomized (SAD + Vx) rabbits. Eight rabbits were anesthetized with pentobarbital sodium. The heart was exposed and suspended in the epicardial cradle. The ABP, HR, and RNA responses were determined when 1 and 10 micrograms/ml BK were applied to the anterior surface of the left ventricle in the intact and SAD + Vx state. In both the intact and SAD + Vx rabbits, ABP, HR, and RNA were significantly reduced with epicardial BK. In the SAD + Vx rabbits, BK evoked small decreases in ABP and HR and no change in RNA after topical lidocaine. These results show the existence of a depressor response and decreases in HR and RNA in the rabbit mediated by the action of BK on cardiac sympathetic afferents.

Afferent Pathways↗

Human left ventricular end-systolic pressure-volume relationship in a cylinder model.

The relationship between myocardial total force and length at the end of systole appears to be linear, and the slope of this relationship is considered to be an appropriate index of myocardial contractile state, independent of preload and afterload. However, direct measurements of this relation may be impossible in the intact human heart, and thus, alternative indices such as the left ventricular end-systolic stress-length, stress-strain, pressure-volume, and pressure-dimension slopes have been proposed to evaluate myocardial contractility in the intact heart. However, the mathematical relationship between the myocardial end-systolic total force-length relation and any of these left ventricular end-systolic relations remains unclear. In this study, assuming a linear myocardial end-systolic total force-length relation in an intact ventricle, we obtained mathematical formulae for the left ventricular end-systolic stress-strain, pressure-radius, and pressure-volume relations, using a cylinder model of the left ventricle. The results obtained using these formulae and the cylinder model were found to match accurately findings obtained from earlier experimental and clinical studies of these left ventricular end-systolic relations. Thus, this model could mathematically account for the relationships between the slopes of the myocardial end-systolic total force-length relation and these left ventricular end-systolic relations.

Blood Pressure↗

Effects of insulin on vasoconstrictive responses to norepinephrine and angiotensin II in rabbit femoral artery and vein.

To determine whether insulin has a vasodilator action on the artery and vein, the effects of insulin at varying concentrations (120 microU/ml, 1.2 mU/ml, 12 mU/ml, and 120 mU/ml) on vasoconstriction by norepinephrine (NE) and angiotensin II (ANG II) were studied in the isolated rabbit femoral artery and vein. Helical strips were suspended in an organ bath filled with modified Krebs solution (pH 7.4), were gassed with 95% O2/5% CO2 at 36 degrees C, and isotonic contractions were measured. Insulin significantly and dose dependently inhibited the vasoconstriction induced by NE (10(-8) M for the artery and 10(-7) M for the vein) at greater than or equal to 1.2 mU/ml for both the artery and vein and the vasoconstriction induced by ANG II (3 x 10(-10) M for the artery and 3 x 10(-9) M for the vein) at greater than or equal to 1.2 mU/ml for the artery and greater than or equal to 12 mU/ml for the vein. The results indicate that insulin has an inhibitory effect on NE- and ANG II-induced contraction in both the artery and vein, and this appeared to be a contributory factor in the hypotensive effect observed in diabetic patients treated with insulin.

Angiotensin II↗

[Left ventricular diastolic properties in dogs evaluated by stress pulsed Doppler echocardiography].

We examined diastolic properties of the left ventricle (LV) of 12 anesthetized open-chest dogs. The heart was paced at a fixed rate of 100 beats/min. The time constant (T) was calculated from the LV pressure curve, and the A/R was measured from LV diastolic velocity curves using pulsed Doppler echocardiography (PDE). Both were used as indexes of the LV diastolic properties. The afterload increased by occluding the descending aorta; the preload decreased by occluding the inferior vena cava. Both T and the A/R increased significantly (p less than 0.01) when the afterload was increased. However, when the preload was decreased, T was not significantly changed. The A/R increased significantly due to a smaller decrement of A than that of R, when the preload was decreased. The percent change of T correlated significantly with that of the A/R, when the afterload was increased (r = 0.687, p less than 0.05). However, there was no correlation between them, when the preload was decreased. We conclude that LV diastolic properties are affected by afterload and preload, and that percent changes of T do not always correlate well with percent changes in the A/R. Thus, it is important to evaluate the preload and afterload states when ever LV diastolic properties are measured clinically.

Animals↗

[Left and right ventricular diastolic properties in essential hypertension during cold pressor test: noninvasive assessment by pulsed Doppler echocardiography].

The diastolic properties of the left and right ventricles of 17 essential hypertensive patients (HT) without left ventricular hypertrophy and of 12 normotensive subjects were assessed by pulsed Doppler echocardiography during the cold pressor test (CPT) and after administration of nifedipine (10 mg). The results were as follows: 1. The peak blood flow velocities due to the left and right atrial contractions (ALV, ARV) at rest in the HT group were significantly greater (p less than 0.001) than those in the control group. The ratios of peak velocities due to atrial contraction and rapid filling of each ventricle (A/R) in the HT group were significantly increased (p less than 0.001) compared with those of the controls. 2. The peak rapid filling flow velocity of each ventricle during cold pressor test in the HT group was significantly less and the A/R of each ventricle was significantly (p less than 0.001) greater compared to those at rest. 3. Diastolic indices and systolic blood pressure did not change significantly after administration of nifedipine at rest or during cold pressor test. These results indicate that abnormal diastolic properties of the left and right ventricles are further deteriorated by increasing afterload.

Adult↗

Antihypertensive treatment in spontaneously hypertensive rats with streptozotocin-induced diabetes mellitus.

Recent clinical reports have suggested that hypertension accelerates the progress of diabetic nephropathy and retinopathy, whereas antihypertensive treatments may retard them. Thus, the effect of antihypertensive treatment in diabetes mellitus with hypertension was evaluated in rats. A model of diabetes mellitus with hypertension has been developed in spontaneously hypertensive (SHR) rats by unilateral nephrectomy and streptozotocin (STZ, 30 mg/kg, i.v. treatment). The rats were treated with four antihypertensive drugs orally for 12 weeks thereafter. STZ treatment induced chronic hypeglycaemia (300-400 mg/dl), decreased body weight and heart rate, and caused vascular changes of ophthalmic fundi and cataracta. The kidney of these rats showed proliferative changes such as periarteritis nodosa, hyperplasia, or fibronecrosis of the arterioles, exudative changes, mesangial proliferation, or thickening of the basement membrane of the glomeruli. Enalapril (10 mg/kg per day) and remipril (Hoe 498) (1 mg/kg per day), converting enzyme inhibitors, or arotinolol (20 mg/kg per day), a beta-adrenoceptor blocking drug, decreased blood pressure, prevented the development of renal and ocular lesions, and tended to increase creatinine clearance. Nisoldipine (3 mg/kg per day), a calcium-entry blocking drug, tended to decrease blood glucose, and prevented the decrease of body weight and development of ocular lesions. In conclusion, antihypertensive treatments were effective in preventing the progress of diabetic retinopathy and nephropathy, and renal insufficiency in this animal model.

Aldosterone↗

High-performance liquid chromatographic system for the rapid purification of growth-hormone receptor in rabbit livers.

A system consisting of high-performance affinity chromatography and size-exclusion chromatography has been developed for the rapid purification and isolation of relatively labile membrane proteins, such as growth-hormone receptor. The crude membrane sample containing growth-hormone receptor was obtained from rabbit livers by ultracentrifugation, followed by solubilization with Triton X-100. The sample was introduced into the high-performance affinity gel column through a large-volume loop injector. After removal of unretained proteins, the fraction containing the growth-hormone receptor was eluted with 6 M urea solution. The eluate from the affinity column passed directly into the size-exclusion gel column, where rapid desalting and separation from contaminants were achieved. The eluate was monitored by UV absorption at 280 nm and fractionated for the subsequent binding assay with 125I-labelled human growth hormone.

Animals↗

Prostaglandins in enhanced pressor response in renal prehypertensive rabbits.

The role of prostaglandins (PGs) in the pressor response to norepinephrine (NE) was examined in one-kidney, one clip rabbits with renal artery stenosis for 3-day's duration (3-day clipped rabbits) and in sham operated rabbits with one-kidney without renal artery stenosis. An exaggerated pressor response to NE, 800 ng/kg/min, was observed in the 3-day clipped rabbits, and it was abolished by angiotensin II antagonist, [Sar1, Ile8] angiotensin II (AIIA). Treatment with indomethacin, 10 mg/kg, induced hyperresponsiveness to NE in the sham operated rabbits and also produced a further increase in the response in the 3-day clipped rabbits: the enhanced responses with similar levels were not attenuated by AIIA in both groups. A subdepressor dose of PGE2, 800 ng/kg/min, abolished the hyperresponsiveness in the 3-day clipped rabbits, while subdepressor or depressor dose of PGI2, 10 or 20 ng/kg/min did not, but the concurrent infusion of AIIA with PGI2 attenuated it. These results indicate that PGs, in particular PGE2 might be involved in the enhanced pressor response to NE in the 3-day clipped rabbits in addition to the altered renin-angiotensin system.

Angiotensin II↗

Non-invasive assessment of the age related changes in stiffness of major branches of the human arteries.

The static mechanical properties of major branches of the human arteries (common carotid artery, abdominal aorta, femoral artery, and brachial artery) were studied in 39 subjects, aged 6-81 years, using an ultrasonic phase locked echo tracking system that allows continuous transcutaneous measurement of the diameter of the artery. The stiffness indices were calculated from the relation between systemic blood pressure and arterial diameter. With advancing age there was a significant increase in the diameter of all arteries with a reduction in percentage change in diameter. The stiffness index increased with age in all arteries; however, in the brachial and femoral arteries there was considerable variation in the individual values for a given age. The age associated increase in stiffness was statistically significant only in the common carotid artery and the abdominal aorta. Although the mechanical properties of the peripheral arteries were significantly influenced by the measuring environment, the calculated stiffness indices were less vulnerable to these stimuli in the central arteries. These results indicate that the stiffness indices of the peripheral muscular arteries are modified appreciably by vasoactive stimuli and that the mechanical properties of the deeper elastic arteries provide sufficiently reliable information about changes caused by aging and arteriosclerosis. The new ultrasonic method used appears to be suitable for this analysis.

Adolescent↗