A transverse emittance and acceptance measurement system in a low-energy beam transport line.

A transverse beam emittance and acceptance measurement system has been developed to visualize the relationship between the injected beam emittance and the acceptance of a cyclotron. The system is composed of a steering magnet, two pairs of slits to limit the horizontal and vertical phase-space, a beam intensity detector just behind the slits for the emittance measurement, and a beam intensity detector in the cyclotron for the acceptance measurement. The emittance is obtained by scanning the slits and measuring the beam intensity distribution. The acceptance is obtained by measuring the distribution of relative beam transmission by injecting small emittance beams at various positions in a transverse phase-space using the slits. In the acceptance measurement, the beam from an ion source is deflected to the defined region by the slits using the steering magnet so that measurable acceptance area covers a region outside the injection beam emittance. Measurement tests were carried out under the condition of accelerating a beam of (16)O(6+) from 50.2 keV to 160 MeV. The emittance of the injected beam and the acceptance for accelerating and transporting the beam to the entrance of the extraction deflector were successfully measured. The relationship between the emittance and acceptance is visualized by displaying the results in the same phase-plane.

Comment on "temperature-dependent localized excitations of doped carriers in superconducting diamond".

A Comment on the Letter by K. Ishizaka et al., Phys. Rev. Lett. 100, 166402 (2008)10.1103/PhysRevLett.100.166402. The authors of the Letter offer a Reply.

Possible association of actin filaments with chloroplasts of spinach mesophyll cells in vivo and in vitro.

In palisade mesophyll cells of spinach (Spinacia oleracea L.) kept under low-intensity white light, chloroplasts were apparently immobile and seemed to be surrounded by fine bundles of actin filaments. High-intensity blue light induced actin-dependent chloroplast movement concomitant with the appearance of a couple of long, straight bundles of actin filaments in each cell, whereas high-intensity red light was essentially ineffective in inducing these responses. The actin organization observed under low-intensity white light has been postulated to function in anchoring chloroplasts at proper intracellular positions through direct interaction with the chloroplasts. Intact chloroplasts, which retained their outer envelopes, were isolated after homogenization of leaves and Percoll centrifugation. No endogenous actin was detected by immunoblotting in the final intact-chloroplast fraction prepared from the leaves kept under low-intensity white light or in darkness. In cosedimentation assays with exogenously added skeletal muscle filamentous actin, however, actin was detected in the intact-chloroplast fraction precipitated after low-speed centrifugation. The association of actin with chloroplasts was apparently dependent on incubation time and chloroplast density. After partial disruption of the outer envelope of isolated chloroplasts by treatment with trypsin, actin was no longer coprecipitated. The results suggest that chloroplasts in spinach leaves can directly interact with actin, and that this interaction may be involved in the regulation of intracellular positioning of chloroplasts.

Characteristic response of plastic track detectors to 40-80 MeV neutrons.

This paper investigates the characteristic response of plastic track detectors to high-energy neutrons. Three types of plastic nuclear track detector (PNTD), Baryotrak made of pure CR-39, TD-1 made of CR-39 containing an antioxidant and TNF-1 made of a copolymer of CR-39/N-isopropylacrylamide, were exposed in quasi-monoenergetic neutron fields generated by p-Li reactions. The total efficiencies for TD-1 and TNF-1 were more than double and triple that of Baryotrak respectively. In addition, the species of particles were classitied into three groups, i.e. proton relatives, alpha particles and heavy ions, by analysing the etch-pit growth curve obtained by step-by-step etching. In a 65 MeV neutron field about half of the tracks recorded in pure CR-39 were due to heavy ions, whereas the TNF-1 detector could effectively register the protons, accounting for 70% of the tracks. The results could be explained by the difference in the sensitivity to high-energy protons.

Interleukin-1beta mediates ischemic injury in the rat retina.

Two types of experiment were performed to examine the role of interleukin-1beta in ischemia-induced damage in the rat retina. In the in vivo study, enzyme-linked immunosorbent assay was used to investigate the expression of immunoreactive interleukin-1beta in the rat retina following a hypertension-induced ischemia/reperfusion, while the effect of a recombinant human interleukin-1 receptor antagonist or an anti-interleukin-1beta neutralizing antibody on the ischemia-induced damage was examined histologically. A transient increase in the expression of immunoreactive interleukin-1beta was observed in the retina 3-12 hr after reperfusion, and morphometric evaluation at 7 days after the ischemia showed a decrease in cell numbers in the ganglion cell layer and a decreased thickness of the inner plexiform layer with no change in the other retinal layers. Intravitreal injection of interleukin-1 receptor antagonist (1 or 10 ng per eye) or anti-interleukin-1beta antibody (50 or 500 ng per eye) 5 min before the onset of the ischemia reduced the damage. In the in vitro study, interleukin-1 receptor antagonist (500 ng ml(-1)) significantly reduced glutamate-induced neurotoxicity in rat cultured retinal neurons. These results suggest that interleukin-1 plays an important role in mediating ischemic and excitotoxic damage in the retina, and that interleukin-1 inhibitors may be therapeutically useful against neuronal injury caused by optic nerve or retinal diseases such as glaucoma and central retinal artery or vein occlusion.

Dual effects of interleukin-1beta on N-methyl-D-aspartate-induced retinal neuronal death in rat eyes.

In this study we determine if interleukin-1beta (IL-1beta) modulates N-methyl-D-aspartate (NMDA)-induced retinal damage. Sprague-Dawley rats were anesthetized with inhalation of halothane, after which a single injection of 5 microl of IL-1beta (0.1 to 10 ng/eye) (and/or IL-1 receptor antagonist (IL-1ra)) for experimental eyes was administered. Two days later (or simultaneously), NMDA (20 nmol) was injected into the vitreous space. One week later, each eye was enucleated and transverse sections were subjected to morphometric analysis. Enzyme-linked immunosorbent assay (ELISA) was conducted for the determination of IL-1beta levels in retina. Immunohistochemical and immunoblot studies were also performed. In eyes that received an intravitreal injection of IL-1beta (0.1 to 10 ng/eye), significant thinning of the inner plexiform layer (IPL) was observed (P<0.05). Immunohistochemical and ELISA studies demonstrated upregulated expression of IL-1beta in retinas that had undergone NMDA injection. Treatment with 10 ng of IL-1ra induced a protective effect against NMDA-induced retinal damage. Pretreatment with IL-1beta induced a significant protective effect on NMDA-induced retinal damage. Our studies suggest that IL-1beta induces neuronal cell death directly, as shown by the protective effects of IL-1ra, but has a protective effect on NMDA-induced retinal damage indirectly after an incubation time of at least 2 days.

Angiopoietin-1 upregulation by vascular endothelial growth factor in human retinal pigment epithelial cells.

PURPOSE: To determine whether vascular endothelial growth factor (VEGF) regulates angiopoietin (Ang)-1 and -2 expression in retinal pigment epithelial (RPE) cells. METHODS: Expression of VEGF, Ang1, and Ang2 in surgically removed human choroidal neovascular membranes (CNVMs) was analyzed by double-label confocal immunofluorescence microscopy. Total RNA was extracted from cultured human RPE cells treated with VEGF for mRNA analysis. Northern blot analysis was performed to examine the time course and dose response of Ang1 and Ang2 mRNA expression. mRNA stability and nuclear run-on analyses were performed. Secreted Ang1 and Ang2 protein levels in conditioned media from RPE cells were examined by Western blot analysis. RESULTS: Ang1 and Ang2 immunostaining colocalized with VEGF-positive stromal cells in human CNVMS: Ang1 and Ang2 mRNAs were expressed by cultured serum-starved RPE cells. VEGF upregulated Ang1 mRNA in a time- and dose-dependent manner without a significant change in Ang2 mRNA. Ang1 and Ang2 mRNAs in RPE cells were as stable as that of S18. VEGF stimulation further increased the half-life of Ang1 mRNA, but did not alter its transcription rate. VEGF increased the amount of Ang1, but not Ang2, protein secreted into the medium. CONCLUSIONS: The colocalization of Ang1 and Ang2 with VEGF in CNVM stromal cells and the upregulation of Ang1 expression by VEGF in cultured RPE cells suggest that VEGF may selectively modulate Ang expression during CNV.

A novel benzothiazine Ca2+ channel antagonist, semotiadil, inhibits cardiac L-type Ca2+ currents.

The influence of semotiadil fumarate, a novel vasoselective Ca2+ channel antagonist with a benzothiazine skeleton, was measured on the high-threshold Ca2+ current ICa,L in guinea-pig ventricular myocytes prepared by coronary perfusion with collagenase solution. Patch- and voltage-clamp methods were used to measure ICa,L. Diltiazem, nifedipine and amlodipine were studied for comparison. Samotiadil could be shown to inhibit ICa,L in a dose-dependent manner in concentrations similar to those of diltiazem but was less effective than amlodipine and nifedipine. The IC50 for nifedipine and amlodipine was in the range between 0.1 and 1 microM and that of semotiadil and diltiazem was between 10 and 100 microM. Recovery from inactivation of ICa,L in the control and under the influence of nifedipine 0.01 microM) and amlodipine (0.1 microM) was complete alter I. Semotiadil (0.1 microM) and diltiazem (1 microM) prolonged the time to full recovery to 20 s. This significant delay in the recovery of ICa,L produced by semotiadil indicates a mode of action similar to that of the verapamil type of Ca2+ channel antagonists and masses a clear distinction between it and the dihydropyridines, which have no effect on the recovery process. The rate dependence of the effect in combination with a distinct influence of the holding potential underlines the use dependence of the mechanism underlying the effect of semotiadil. The well-known high vasoselectivity of semotiadil in combination with a relatively low Ca2+ channel antagonistic influence on the heart makes semotiadil an interesting candidate for the treatment of coronary heart diseases.

Effects of semotiadil, a novel Ca2+ channel antagonist, on the electrical activity of Langendorff-perfused guinea pig hearts in comparison with diltiazem, amlodipine and nifedipine.

Semotiadil, a new Ca2+ antagonist with a high vasoselectivity, in high concentrations depresses AV nodal conduction in a frequency-dependent manner. The aim of the present study was to investigate the effects of semotiadil on intact cardiac conduction and the pacemaker system in comparison with diltiazem, amlodipine and nifedipine. The effects were studied in isolated guinea pig hearts perfused by the method of Langendorff. Both semotiadil and diltiazem decreased markedly the sinus rate in a concentration-dependent manner whereas this was not the case in the presence of amlodipine and nifedipine. Semotiadil (10 microM) markedly prolonged sinus node recovery time and in the presence of diltiazem (10 microM) in 5 out of 7 experiments an intermittent sinus node arrest occurred. Atrioventricular conduction and the effective refractory period of the AV node were most affected by diltiazem and semotiadil. The Ca2+ channel blocking compound semotiadil showed the most pronounced rate-dependent effects on the AV node. In the presence of diltiazem the QT interval became even shorter than in untreated hearts. In contrast, semotiadil did not act on the QT interval. In conclusion, as semotiadil exerts a clear rate-dependent effect on AV nodal conduction with a long time constant, it mimics the electrophysiological behavior of a substance of the verapamil type.

Characteristics of human immunodeficiency virus and chlorpromazine induced antiphospholipid antibodies: effect of beta 2 glycoprotein I on binding to phospholipid.

OBJECTIVE: To investigate the nature of the target epitope for human immunodeficiency virus (HIV) and chlorpromazine (CPZ) induced antiphospholipid antibodies (aPL) by evaluating the effect of the aPL cofactor (beta 2 glycoprotein I) on phospholipid binding and to compare this with known binding patterns of infection induced and autoimmune aPL. METHODS: aPL positive sera from 17 patients with HIV and 16 patients with schizophrenia treated with CPZ were tested and compared with aPL positive sera from 20 patients with syphilis and 35 with autoimmune disease. Both the sera and either IgG fractions prepared by affinity chromatography or IgM fractions prepared by euglobulin precipitation and gel filtration were tested for binding to cardiolipin (CL) in ELISA in the presence and absence of purified human beta 2 glycoprotein I (beta 2-GPI). Competition studies evaluated biotinylated CPZ IgM aPL binding and the effect on this of added aPL, placental anticoagulant protein I--a phospholipid binding protein that inhibits autoimmune aPL--and CL vesicles. RESULTS: HIV IgG aPL binding to CL was inhibited by beta 2-GPI (51-53%), like syphilis IgG aPL and in contrast to autoimmune IgG aPL. CPZ IgM aPL, like autoimmune IgM aPL, bound more efficiently in the presence of beta 2-GPI, with binding increases of 31-149%. Binding of biotinylated CPZ IgM aPL to CL was competitively inhibited by autoimmune IgG aPL (47%) and CPZ aPL (92%) but not by HIV IgG aPL or normal IgG. Placental anticoagulant protein I and CL vesicles completely prevented binding of CPZ IgM aPL to CL (100 and 96% inhibition, respectively). CONCLUSIONS: Findings indicate that CPZ aPL resembles the autoimmune aPL, whereas aPL found in HIV infection do not appear to be of autoimmune type.

Antihypertensive effect of a novel calcium antagonist, SD-3211, in experimental hypertensive rats.

The antihypertensive effect of SD-3211, a structurally novel type of nondihydropyridine calcium antagonist, was assessed using several types of experimental hypertensive rats. Oral administration of SD-3211 (10, 20, and 30 mg/kg) to conscious spontaneously hypertensive rats (SHR), deoxycorticosterone acetate-salt hypertensive rats (DHR) and 2-kidney, 1-clip renal hypertensive rats (RHR) resulted in a dose-dependent decrease in systolic blood pressure (SBP). The hypotensive effect of SD-3211 in these hypertensive rats was more pronounced than in normotensive rats (NR). The potencies of SD-3211 for the hypotensive effect in the hypertensive rats and NR were 5-7 times greater than that of diltiazem but 2-3 times less than that of nicardipine. Furthermore, SD-3211 showed longer-lasting hypotensive action than diltiazem and nicardipine, at the respective equihypotensive dose. During the course of hypotension, SD-3211 did not exert any influence on heart rate (HR) in any type of hypertensive rats or NR, in contrast to the appearance of tachycardia with nicardipine in SHR, DHR, and NR and of bradycardia with diltiazem in DHR. At doses of 10 and 30 mg/kg, the hypotensive doses, SD-3211 elicited a dose-dependent natriuresis but no kaliuresis in SHR. In the chronic study using SHR, SD-3211 at 10 mg/kg/day showed an antihypertensive effect during an administration period of 12 consecutive weeks. These results allow us to conclude that SD-3211 has a potent and long-lasting hypotensive action with little cardiac effect.

Anti-ischaemic and vasospasmolytic effects of a novel Ca2+ channel blocker, SD-3211, in vitro.

1. The present study was undertaken to determine the vasospasmolytic activity of a novel non-dihydropyridine type of Ca2+ channel blocker, SD-3211, in isolated canine coronary arteries and its ability to reduce myocardial ischaemic damage in isolated perfused rabbit hearts. 2. The vasospasmolytic effect of SD-3211 was investigated using 3,4-diaminopyridine-induced rhythmic contraction, in comparison with its enantiomer (SD-3212), nicardipine and diltiazem. SD-3211 was shown to reduce the peak tension and increase the contraction frequency. The order of potency for the relaxation of the peak tension was as follows: nicardipine greater than SD-3211 greater than diltiazem greater than SD-3212 and being compatible with that for the relaxant effects of these compounds on KCl-induced contraction in the same specimen. 3. Furthermore, the effect of SD-3211 on myocardial damage due to global ischaemia for 60 min followed by 60 min of reperfusion was examined. SD-3211 at a concentration of 2 X 10(-8) mol/L was given for 40 min before and again for 60 min after the ischaemia. SD-3211 attenuated the increase in leakage of creatine phosphokinase from the hearts and the decrease in pH of perfusate during reperfusion, while concomitantly providing a significant improvement in the post-ischaemic recovery of developed tension. 4. These results suggest that SD-3211 has properties to reduce coronary vasospasm and to provide protection against ischaemic damage, both of which may have beneficial actions in the treatment of ischaemic heart disease.

Cardiohemodynamic effect of a novel calcium antagonist, SD-3211, in the dog.

The cardiohemodynamic effects of SD-3211, a calcium antagonist possessing a unique structure, were studied in anesthetized open-chest dogs and in conscious dogs. SD-3211 (10-300 micrograms/kg, i.v.) increased coronary and vertebral artery blood flow dose-dependently while lowering blood pressure, indicating a vasodilatation of these arteries. SD-3211 caused a significant increase in heart rate at 10-100 micrograms/kg, but a significant decrease at 300 micrograms/kg. Left ventricular dp dtmax was dose-dependently decreased at the dose range examined, and the change was significant at 300 micrograms/kg. When compared with the cardiohemodynamic effects of diltiazem (10 300 micrograms/kg, i.v.) and nicardipine (1-30 micrograms/kg, i.v.), the selectivity of SD-3211 with regard to vasodilatation as compared to cardiac depression, manifested by a reduction in heart rate and myocardial contractility, was greater than that of diltiazem, but less than that of nicardipine. Furthermore, a comparative study of the effects of orally administered SD-3211 and diltiazem on blood pressure and atrioventricular conduction in conscious, normotensive dogs, demonstrated that SD-3211 had a more potent and long-lasting hypotensive effect, but a much weaker effect on atrioventricular conduction prolongation than diltiazem. Thus, these in vivo cardiohemodynamic studies show that SD-3211 possesses a tissue-selectivity for vasculature, respectively cardiac tissues, which is intermediate between diltiazem and nicardipine.

Cardiovascular characterization of SD-3211, a novel benzothiazine calcium channel blocker, in isolated rabbit hearts.

The cardiovascular effects of SD-3211, a novel benzothiazine Ca++ channel blocker, were compared with those of diltiazem and nicardipine in Langendorff-perfused rabbit hearts. SD-3211 was more potent in increasing coronary artery flow than in depressing cardiac function (i.e., contractile force, heart rate and conduction time). The relative specificity of SD-3211 for coronary vasodilation to cardiodepression was clearly greater than that of diltiazem, but less than that of nicardipine. Thus, the present study demonstrates that SD-3211, despite a non-dihydropyridine type of Ca++ channel blocker, can be characterized as a potent coronary vasodilator with a little effect on cardiac function.

SD-3211, a novel benzothiazine calcium antagonist, alone and in combination with a beta-adrenoceptor antagonist, produces antihypertensive effects without affecting heart rate and atrioventricular conduction in conscious renal hypertensive dogs.

We compared the effects of SD-3211, a novel calcium antagonist, on blood pressure, heart rate, and atrioventricular conduction with those of diltiazem using conscious renal hypertensive dogs (one-kidney, one-clip type). We also examined the combined effects of these calcium antagonists with a beta-adrenoceptor antagonist, propranolol, on these variables. Oral administration of SD-3211 (1.25, 2.5, and 5 mg/kg) resulted in a dose-dependent decrease in blood pressure without affecting heart rate. SD-3211 at all three doses significantly decreased systolic blood pressure. At 2.5 and 5 mg/kg the compound elicited significant decreases in mean blood pressure and diastolic blood pressure. Hypotension obtained with the highest dose of SD-3211 lasted for at least 9 h. No significant alteration in PR interval was observed in electrocardiograms after administration of SD-3211. Diltiazem, given orally at doses of 2.5 and 5 mg/kg but not 1.25 mg/kg, produced significant hypotension with little change in heart rate. The duration of hypotension induced by the highest dose of diltiazem was only 3 h. Diltiazem prolonged PR interval in a dose-dependent manner, causing second-degree atrioventricular block in some dogs. Combined administration of SD-3211 or diltiazem (2.5 mg/kg) with propranolol (30 mg/kg) resulted in enhanced hypotension with no alteration in heart rate. SD-3211 plus propranolol had little effect on the PR interval, whereas diltiazem plus propranolol caused a markedly enhanced prolongation. These results indicate that SD-3211 is an antihypertensive agent with long-lasting action and little effect on heart rate and atrioventricular conduction and, when administered alone or in combination with propranolol, may be useful in the treatment of hypertension.

Electrophysiological properties of SD-3211, a novel putative Ca2+ antagonist, in isolated guinea pig and rabbit hearts.

The cardiac effects of SD-3211, a novel non-dihydropyridine type of Ca2+ antagonist, were examined in isolated guinea pig and rabbit hearts using an electrophysiological technique. SD-3211 (10(-6)-10(-5) M) shortened the action potential duration of guinea pig papillary muscles in a concentration-dependent manner without affecting the resting potential or the maximum upstroke velocity (Vmax). The Vmax of slow responses induced by high extracellular K+ and isoproterenol was inhibited by SD-3211 at concentrations of greater than 10(-6) M. Elevation of extracellular Ca2+ by 2 mM reversed this inhibited response. The inhibitory effect of SD-3211 on the slow response was enhanced as the stimulation frequency was increased. In Langendorff-perfused rabbit hearts electrically driven at 2.0 Hz, SD-3211 (10(-8)-10(-6) M) produced a concentration-dependent prolongation of the atrium-His bundle conduction time (A-H interval) as well as a reduction in the developed tension of ventricular muscle, whereas SD-3211 did not affect the His bundle-ventricular conduction time (H-V interval) significantly. The potency of SD-3211 in A-H prolongation was greater than those of diltiazem and bepridil, but weaker than those of nicardipine, nifedipine, and verapamil. The effect of SD-3211 on the A-H interval was more pronounced at higher stimulation frequencies. SD-3211 was intermediate between nicardipine and verapamil in its intensity of frequency-dependent effects on the A-H interval. These results suggest that SD-3211 has a preferential and frequency-dependent inhibitory action on cardiac slow Ca2+ channels.

Tissue selectivity of the novel calcium antagonist sesamodil fumarate in isolated smooth muscles and cardiac muscles.

The effects of the novel Ca2+ antagonist sesamodil fumarate (JAN), (+)-3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[(3,4- methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo-2H- 1,4-benzothiazine hydrogen fumarate (SD-3211), on isolated smooth muscles and cardiac muscles were investigated and compared with those of diltiazem, verapamil, nifedipine and nicardipine. Ca2+ antagonistic activity of SD-3211 (pA2 = 8.42) was more potent than that of diltiazem and verapamil, but less potent than that of nifedipine and nicardipine in isolated pig coronary artery. The inhibition of Ca2(+)-induced contraction by SD-3211 was not reversed by drug washout, whereas that by diltiazem was easily reversed by drug washout. SD-3211 produced a concentration-dependent relaxation (EC50 = 5.7 x 10(-8) mol/l) of KCl-contracted pig coronary artery. The order of potency of the various compounds correlated with their respective Ca2+ antagonistic activities. SD-3211 antagonized KCl-induced contraction, but not that induced by A23187, in the rabbit aorta. On the other hand, negative inotropic and chronotropic effects of SD-3211 on the guinea pig right atria approximated those of diltiazem and verapamil. These results suggest that SD-3211 exerts a potent and long-lasting Ca2+ antagonistic effect on isolated arteries, possessing pharmacological properties diverse from those of known Ca2+ antagonists with respect to tissue selectivity, i.e., it is more vasoselective than diltiazem and verapamil, and more cardioselective than nifedipine and nicardipine.

Electrophysiologic effects of a novel Ca antagonist, SA2572, in isolated rabbit and guinea pig hearts.

Cardiac effects of SA2572, a newly synthesized Ca antagonist, were evaluated in guinea pig and rabbit hearts with electrophysiologic technique. SA2572(10(-6)-10(-5) M) decreased the upstroke velocity (Vmax) and the duration of the action potential (APD30) in guinea pig papillary muscles in a concentration- and frequency-dependent manner without affecting the resting potential. The slow responses (high K+ + isoproterenol) were suppressed by SA2572 at 10(-6) M. In rabbit sinus node, SA2572(10(-7)-5 x 10(-6) M) caused a concentration-dependent decrease in the amplitude and Vmax of the action potential and tended to prolong the spontaneous cycle length. In Langendorff-perfused rabbit hearts electrically driven at 2 Hz, SA2572(5 x 10(-8)-10(-6) M) produced concentration-dependent prolongations of the atrio-His bundle conduction time (A-H interval) and the His bundle-ventricular conduction time (H-V interval) concomitantly with a reduction of the developed tension of the ventricular muscle. These effects of SA2572 on the A-H and H-V intervals were more pronounced at higher stimulation frequency. Enantiospecificity was observed in these actions of SA2572, (-)-isomer of SA2572 having more potent inhibitory effects on slow channel-dependent than on fast channel-dependent phenomena. These results indicate that SA2572 has characteristics of both slow and fast channel blockers, and that these inhibitory effects are frequency dependent.

Effects of arotinolol, an alpha- and beta-adrenoceptor antagonist, on renin release from rat kidney cortical slices.

The effects of arotinolol on changes in renin release in rat kidney cortical slices in response to isoproterenol (IP) or norepinephrine (NE), were studied in comparison with those of AC-623, a main metabolite of arotinolol, and other typical adrenoceptor antagonists. Arotinolol, at concentrations of 10(-8) to 10(-4) mol/l, inhibited the increasing effect of 10(-6) mol/l IP on renin release, in a concentration-dependent manner. Similar results were observed with AC-623, propranolol or labetalol, although the inhibitory potencies of these agents were considerably lower than that of arotinolol. The blocking effect of arotinolol on the 10(-5) mol/l NE-induced decrease in renin release was much less potent than seen with other alpha-adrenoceptor blocking agents such as prazosin, phenoxybenzamine and labetalol. These data suggest that the potent blocking effects of arotinolol and its metabolite on the increased renin release in response to beta-adrenoceptor stimulation may contribute to the antihypertensive effect of this agent.