Bunazosin Hydrochloride Research Articles

Topical Application of Bunazosin Hydrochloride Suppresses Myopia Progression With an Increase in Choroidal Blood Perfusion.

The incidence of myopia has rapidly increased in recent decades, making it a growing public health concern worldwide. Interventions to suppress the progression of myopia are needed; one suggested strategy is the prevention of choroidal thinning, which can improve choroidal blood perfusion (ChBP). Bunazosin hydrochloride (BH) is an alpha1-adrenergic blocker and commercialized glaucoma eye drop that increases in blood circulation in the eye. In this study, we evaluated the efficacy of BH in suppressing the progression of myopia in a lens-induced murine model. Lens-induced myopia was induced in 3-week-old C57BL/6 J mice with -30 diopter (D) lenses for three weeks. Refractive error, axial length, and choroidal thickness were evaluated at three and six weeks of age using an infrared photorefractor and a spectral domain optical coherence tomography (OCT) system. Moreover, ChBP and scleral thickness were evaluated using swept-source OCT and histological analysis. Compared with the controls, the administration of BH eye drops suppressed the myopic shift of refractive error (mean difference ± standard error in the eye with -30D lens, -13.65 ± 5.69D vs. 2.55 ± 4.30 D; P<0.001), axial elongation (0.226 ± 0.013 mm vs. 0.183 ± 0.023 mm; P<0.05), choroidal thinning (-2.01 ± 1.80µm vs. 1.88 ± 1.27µm; P<0.001), and scleral thinning (11.41 ± 3.91µm vs. 19.72 ± 4.01µm; P<0.01) with myopia progression and increased ChBP (52.0% ± 4.1% vs. 59.5% ± 6.3%; P<0.05). The suppressive effect of BH eye drops was dose-dependent and higher than that of other glaucoma eye drops and alpha1 blockers. These results demonstrate the potential of BH eye drops in the treatment of myopia and support further investigation of their efficacy in humans. Further studies are needed to determine the mechanism of action and long-term safety of this treatment.

Effect of egg yolk lecithin on transdermal delivery of bunazosin hydrochloride.

Transdermal delivery of bunazosin HCl and the enhancing effect of egg yolk lecithin were examined using an in-vitro hairless mouse skin preparation and rabbits for in-vivo systemic absorption. The delivery of bunazosin in-vitro was small, but it was significantly enhanced when lecithin was incorporated into the same vehicle. This enhancing effect was confirmed with other drugs in-vitro. The enhancing ability was also seen in-vivo. Very little bunazosin was delivered from a propylene glycol suspension, but levels of 100-200 ng mL-1 were achieved by the incorporation of the lechithin.

Effects of adrenergic and cholinergic antagonists on diameter of nasolacrimal drainage system

To determine the effect of an adrenergic and a cholinergic antagonist on the diameter of the lumen of the nasolacrimal drainage system. The asymptomatic side of 38 patients (29 women, nine men) with unilateral stenosis/obstruction of the nasolacrimal drainage system was studied. The tear meniscus height (TMH) of the asymptomatic side was normal, and the lacrimal drainage system was patent as revealed by dacryocystography. The nasolacrimal drainage system of the asymptomatic side was infused with 100 mul of 0.01% bunazosin hydrochloride, a selective alpha-1 adrenergic antagonist, or 100 mul of 0.4% tropicamide, a muscarinic and cholinergic antagonist. Dacryocystography was performed to determine the diameter of the lumen of the nasolacrimal drainage system before and after the antagonists. Bunazosin reduced the diameter of the lumen significantly, and the changes were more marked in the nasolacrimal duct (NLD), especially the middle and the lower regions. The diameter of the lumen of the lacrimal sac was not changed significantly. In contrast, tropicamide did not cause any significant change in the diameter of the lumen of the nasolacrimal drainage system. The alterations of the size of the lumen of the nasolacrimal drainage system, especially the NLD, by an adrenergic antagonist suggest that the lumen diameter is under continuous sympathetic tone, and the parasympathetic tone is weak.

Acute crisis of hypertension, tachycardia and flush of Amyotrophic lateral sclerosis

We present a rare case of ALS with acute crisis of severe hypertension, tachycardia and flush. Although he showed those attacks several times, we were able to successfully control those symptoms using daily diazepam and bunazosin hydrochloride, alpha receptor antagonist. Since not only neurologist but also many family physicians have been a chance to see and care for ALS individuals, we have to become aware of the presence of severe autonomic dysfunction of cardiovascular system in the individuals of ALS.

Addition of or Switch to Topical Bunazosin Hydrochloride in Elderly Patients with Normal-Tension Glaucoma: A One-Year Follow-up Study

To evaluate the efficacy and safety of 0.01% bunazosin hydrochloride ophthalmic solution (bunazosin) for elderly patients with normal-tension glaucoma (NTG) as an addition to or instead of their previous therapy. Bunazosin was administered to NTG patients aged 65 years or over who had been undergoing topical glaucoma therapy. In accordance with the study protocol, intraocular pressure (IOP) and visual field measurement were performed and the safety of the treatment was evaluated periodically between week 0 and week 52 at the five facilities where the study was carried out. Of the 98 enrolled patients, 84 (85.7%) were followed up for 52 weeks. During the follow-up period, IOP significantly and persistently decreased (week 0, 15.0 +/- 2.5 mmHg; week 52, 13.4 +/- 2.4 mmHg, P < 0.0001), but the decrease in mean deviation (MD) was not significant. Although no systemic adverse reactions were observed, local adverse events were noted in 7 of the 98 patients. The addition of or the switch to bunazosin in elderly NTG patients resulted in a significant reduction of IOP without apparent exacerbation of visual field defects or systemic or local adverse reactions other than conjunctival hyperemia.

An .ALPHA.1-Receptor Blocker Reduces Plasma Leptin Levels in Hypertensive Patients with Obesity and Hyperleptinemia

Obesity is often complicated by hypertension, and both conditions are risk factors for atherosclerosis. Leptin has attracted attention as a possible cause of hypertension in obese persons. We investigated the effect of a slow-release alpha1-receptor blocker, bunazosin hydrochloride, on leptin levels and insulin resistance in obese hypertensive patients with hyperleptinemia. The subjects were 17 patients (12 men and 5 women aged 56.1 +/- 12.2 years) with essential hypertension who were not receiving alpha1-receptor blockers. They had a body mass index (BMI) > or = 25 kg/m2 and a plasma leptin concentration > or = 5 ng/ml. They received oral therapy with bunazosin hydrochloride at doses of up to 9 mg/day. The plasma leptin concentration, body weight, blood pressure, heart rate, fasting blood glucose, plasma insulin concentration, and free fatty acid level were compared between before and after treatment. Although there was no significant change of BMI, there was a significant decrease of plasma leptin after treatment (10.6 +/- 5.4 ng/ml vs. 8.7 +/- 3.4 ng/ml, p = 0.0128), as well as a significant decrease of plasma insulin (9.8 +/- 4.8 microU/ml vs. 8.1 +/- 4.6 microU/ml, p = 0.0494) and HOMA-R (2.9 +/- 2.1 vs. 2.2 +/- 1.5, p = 0.0237). In conclusion, bunazosin hydrochloride reduced the plasma leptin level and improved insulin resistance in hypertensive patients with obesity and hyperleptinemia.

Bunazosin, a Selective α1 ‐Adrenoceptor Antagonist, as an Anti‐glaucoma Drug: Effects on Ocular Circulation and Retinal Neuronal Damage

Bunazosin hydrochloride is a potent and selective alpha1-adrenoceptor antagonist that has been clinically used both as a systemic antihypertensive as well as an ocular hypotensive drug. In a number of studies, we have examined some effects of bunazosin hydrochloride that might indicate its potential as an anti-glaucoma drug. In normal rabbit eyes, topically instilled bunazosin hydrochloride reached the posterior retina by local penetration at concentrations sufficient to attenuate the phenylephrine- or endothelin-1 (ET-1)-induced constriction of retinal arteries. Furthermore, bunazosin hydrochloride improved the impairment of optic nerve head (ONH) blood flow, the prolongation of visual-evoked potentials (VEP) implicit time, the enlargement of the optic disk cup, and the decrease in the number of retinal ganglion cell layer cells induced by repeated injections of ET-1 in rabbits. Topically instilled bunazosin hydrochloride improved the reductions in ONH capillary blood flow and VEP amplitude induced in rabbit eyes by nitric oxide synthase inhibition. In rat primary retinal cultures, bunazosin hydrochloride reduced glutamate-induced neuronal cell death, presumably through a Na+ channel blocking effect. In healthy humans, topically instilled bunazosin hydrochloride reportedly increases blood velocity in the ONH, retina and choroid, without significantly altering either blood pressure or heart rate. These results indicate that bunazosin hydrochloride exerts both an improvement effect within the ocular circulation and a direct neuroprotective effect. Hence, bunazosin hydrochloride may be useful as a therapeutic drug against ischemic retinal diseases (such as glaucoma and retinal vascular occlusive diseases) that are associated with disturbances of the ocular circulation.

Amelioration of Endothelin-1–Induced Optic Nerve Head Ischemia by Topical Bunazosin

Purpose: To investigate the effects of bunazosin hydrochloride, an α1-adrenergic blocker, on the impairment of optic nerve head (ONH) blood flow and depression of visual function induced by repeated intravitreal injections of endothelin-1 (ET-1) in rabbits. Method: We injected ET-1 (20 pmol) into the right posterior vitreous of rabbits twice a week for 4 weeks, and the observation period was set at 8 weeks (starting from the first injection). The animals that received ET-1 were divided into two groups: twice a day for 8 weeks, one group received topical 0.01% bunazosin, while the second received the vehicle for bunazosin. The ONH blood flow was monitored using the laser speckle method, and visual function was assessed by examining visually evoked potentials (VEPs). Changes in the ONH cup/disk area and in the number of cells in the retinal ganglion cell layer (GCL) were also determined.Results: Repeated injections of ET-1 decreased the ONH blood flow, prolonged the VEP implicit time, enlarged the optic cup, and decreased the number of GCL cells. Topical bunazosin significantly decreased these impairments. Conclusions: These results indicate that in rabbits, topical bunazosin suppresses the changes in ONH circulation and function induced by intravitreal ET-1.

Effects of Topically Instilled Bunazosin, an α1-Adrenoceptor Antagonist, on Constrictions Induced by Phenylephrine and ET-1 in Rabbit Retinal Arteries

To examine the inhibitory effects of topically instilled bunazosin hydrochloride (bunazosin), a selective alpha1-adrenoceptor antagonist, on the retinal artery constrictions induced by intravitreous phenylephrine hydrochloride (phenylephrine) and endothelin (ET)-1 in rabbits. Phenylephrine or ET-1 (20 microL) was injected into the central part of the vitreous in both eyes in pigmented rabbits. Color fundus photographs were taken at 5 minutes before and 60 minutes after the injection. The average diameter of the major retinal arteries at the rim of the optic nerve head (ONH) was normalized with respect to ONH diameter. Bunazosin was instilled into one eye (chosen randomly) and vehicle into the fellow eye at 60 minutes before the intravitreous injection. To examine any interaction between the alpha1-adrenoceptor and ET receptor, phenylephrine and ET-1 were co-injected at individually ineffective doses. In addition, ET-1-induced vasoconstriction was examined after unilateral superior cervical ganglionectomy. The binding affinities of bunazosin for ETA and ETB receptors were also evaluated. The series of experiments was performed as masked tests. Retinal arteries were dose-dependently constricted by both intravitreous phenylephrine and intravitreous ET-1. Topically instilled bunazosin at 0.01% partly inhibited both of these vasoconstrictions on the ipsilateral side, but not on the contralateral side. Bunazosin did not bind to ET receptors. Co-injection of phenylephrine and ET-1 at individually ineffective doses constricted retinal arteries significantly. An adrenergic supersensitivity in retinal arteries was observed after superior cervical ganglionectomy only on the ganglionectomized eye. The ET-1-induced vasoconstriction was significantly weaker in cervical ganglionectomized eyes than in sham-surgery eyes. The present findings suggest that topically instilled bunazosin reaches the posterior retina by local penetration at concentrations sufficient to attenuate the phenylephrine- or ET-1-induced constriction of retinal arteries in normal rabbit eyes, and that the inhibitory effect of bunazosin on the ET-1-induced vasoconstriction in this tissue may be partly attributable to an interaction between the alpha1-adrenoceptor and ET receptor.

Effects of bunazosin hydrochloride on ciliary muscle constriction and matrix metalloproteinase activities.

To clarify the mechanism by which bunazosin hydrochloride (BZ), a selective alpha1-adrenoceptor antagonist, increases uveoscleral outflow. The effects of BZ on matrix metalloproteinase (MMP) activities in cultured monkey ciliary muscle cells, and on phenylephrine hydrochloride-induced constriction in bovine ciliary muscles, were examined. Also, the possible additive ocular hypotensive effects of BZ and latanoprost (LP) were evaluated in ocular normotensive monkeys. Although BZ at 10 to 10 M did not increase MMP-2, -3, and -9 activities in the culture medium of ciliary muscle cells, BZ at 10 to 10 M inhibited phenylephrine hydrochloride-induced constriction in ciliary muscles. The maximal reduction in intraocular pressure of concomitant administration of BZ and LP was greater than that of BZ alone and tended to be greater than that of LP alone. These findings, in normotensive monkeys, indicate that the mechanism whereby BZ increases uveoscleral outflow is independent of an effect on MMPs and is partly due to relaxation of the ciliary muscle. This effect is different from that of LP, which might help to explain the finding that topical concomitant administration of BZ and LP increased AUC(0-6h) value (IOP reduction) to 201% and 145% of BZ and LP given alone, respectively.

Bunazosin hydrochloride reduces glutamate-induced neurotoxicity in rat primary retinal cultures

To study neuroprotective effects of bunazosin hydrochloride which is an α 1-adrenoceptor antagonist used as an ocular hypotensive drug compared to other α 1-adrenoceptor antagonists, and its mechanism of action. We evaluated the neuroprotective effects of bunazosin hydrochloride or seven other α 1-adrenoceptor antagonists against glutamate-induced cell death in rat primary retinal cultures. We also evaluated the binding inhibition of bunazosin hydrochloride for 24 different receptors/channels and its effects on the Na + influx into cells induced by veratridine or glutamate. Bunazosin hydrochloride significantly inhibited glutamate-induced cell death at concentrations of 1 and 10 μM. Cells were also protected when treated with some α 1-adrenoceptor antagonists, but not by the others. Bunazosin hydrochloride showed a high inhibition for Na + channels and inhibited the Na + influx induced by veratridine or glutamate. These findings indicate that in retinal cultures bunazosin hydrochloride has a neuroprotective effect against glutamate-induced cell death and that the inhibition of Na + channels by bunazosin hydrochloride may be partly responsible for this effect.

Amelioration by topical bunazosin hydrochloride of the impairment in ocular blood flow caused by nitric oxide synthase inhibition in rabbits.

We investigated whether topical instillation of an alpha(1)-adrenergic blocker would improve an insufficient blood supply in the optic nerve head (ONH) and visual function, in rabbits. The effect of systemic NOS inhibition on visual-evoked potentials (VEPs) and hemodynamics in ONH were determined. VEPs were recorded before and every 15 min during a 120-min observation period after an intravenous injection of 50 mg/kg N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. Capillary blood flow in ONH was evaluated by the laser speckle method throughout the same period. Then, we investigated the effect of topical instillation of a recently developed alpha(1) adrenergic blocker, bunazosin hydrochloride (0.01%), 60 min prior to the intravenous L-NAME (50 mg/kg) on the changes by NOS inhibition. The VEP amplitudes were reduced by L-NAME (10, 20, and 50 mg/kg) in a dose-dependent manner, while the VEP implicit time was unchanged, and no significant changes were detected in the electroretinogram. The reductions in ONH capillary blood flow and VEP amplitudes caused by L-NAME (50 mg/kg) were significantly suppressed by an instillation of bunazosin hydrochloride. These results indicate that blocking alpha(1)-adrenergic receptors may ameliorate the impairments in blood flow and retinal function caused by NOS inhibition. The enhancement of basal vascular tone due to deprivation of continuous NO production may be diminished by this alpha(1)-adrenergic blocker.

Bunazosin hydrochloride inhibits exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats by suppressing the response to growth factors.

Selective alpha1-adrenoreceptor blockers were recently reported to have an in vivo antiproliferative effect on hypertensive cardiovascular organs. Cultured vascular smooth-muscle cells (VSMCs) from spontaneously hypertensive rats (SHRs) show exaggerated growth compared with cells from Wistar-Kyoto (WKY) rats. We investigated the effects of an alpha1-adrenoreceptor blocker, bunazosin hydrochloride (HCl), on the growth of VSMCs from SHRs. In the absence of serum, bunazosin HCl significantly inhibited basal DNA synthesis by VSMCs from SHRs, but not by cells from WKY rats. In the presence of serum, bunazosin HCl significantly inhibited DNA synthesis by VSMCs from both rat strains. Angiotensin (Ang) II, platelet-derived growth factor (PDGF)-AA, and epidermal growth factor (EGF) dose-dependently increased DNA synthesis by VSMCs from SHRs, but not by VSMCs from WKY rats. Bunazosin HCl significantly suppressed the response of DNA synthesis to PDGF-AA and EGF, but not to Ang II, in VSMCs from SHRs. Expression of basic fibroblast growth factor (bFGF), transforming growth factor-beta1 (TGFbeta1), and PDGF messenger RNA (mRNA) was markedly greater in VSMCs from SHRs than in cells from WKY rats. Bunazosin HCl significantly inhibited the expression of bFGF and TGFbeta1 mRNA in VSMCs from SHRs, but not in cells from WKY rats. These findings suggest that the inhibition of growth factor hyperresponsiveness and inhibition of the expression of growth factors in VSMCs from SHRs are associated with the antiproliferative effect of bunazosin.

Bunazosin reduces intraocular pressure in rabbits by increasing uveoscleral outflow.

The mechanism of the ocular hypotensive effect of bunazosin hydrochloride (an alpha1-adrenergic antagonist) and the possible intermediary role of prostaglandins were studied in New Zealand albino rabbits. Aqueous flow, outflow facility and uveoscleral outflow were determined by fluorophotometry, and intraocular pressure (IOP) was measured by pneumatonometry on the fourth day of twice daily topical treatment with 0.1% bunazosin. Uveoscleral outflow was measured with a tracer infusion technique at 1 to 2 hours after one dose of 0.1% bunazosin. Total outflow facility was measured by a two-level constant-pressure infusion method before and at one hour after one dose of 0.1% bunazosin. The effect of topically applied cyclooxygenase inhibitors, including 0.25% indomethacin and 0.03% flurbiprofen, on the IOP reduction after bunazosin was evaluated. At 3 hours after the seventh consecutive dose given twice-daily, bunazosin significantly (P<0.001) reduced IOP to 13.4+/-0.8 mm Hg (mean +/- SEM) from a baseline of 19.6+/-1.1 mm Hg. Indomethacin significantly inhibited the IOP reduction after one dose of bunazosin, whereas flurbiprofen did not (repeated measures ANOVA). Bunazosin significantly increased uveoscleral outflow (P<0.05) and total outflow facility (P<0.02), but not fluorophotometric outflow facility or aqueous flow. It is concluded that, in rabbits, 0.1% bunazosin reduces IOP predominantly by increasing uveoscleral outflow. The role of prostaglandins in this effect is equivocal.

Adrenoceptors affect accommodation by modulating cholinergic activity

In an attempt to clarify the functional role of adrenoceptors in accommodation, the effects of various adrenergic agents on the state of accommodation were studied. Fifty-two emmetropic, visually normal subjects (24.6 ± 0.42 years old) participated in this study. Using an infrared optometer, the far and near points of accommodation were measured by a quasistatic method. Tonic accommodation and accommodative adaptation were also investigated. All these parameters were measured before and after topical application of various adrenergic agents. Both bunazosin hydrochloride (0.1%) and phenylephrine hydrochloride (5%) had no effect on tonic accommodation and accommodative adaptation. However, bunazosin hydrochloride increased the near point of accommodation. Timolol maleate (0.5%) and isoproterenol hydrochloride (3.0%) did not affect tonic accommodation. Isoproterenol hydrochloride evoked a hyperopic shift of the far point of accommodation by 0.23 ± 0.42 diopters (D). Additionally, accommodative adaptation was increased by timolol maleate (0.36 ± 0.62 D) and decreased by isoproterenol hydrochloride (0.18 ± 0.48 D). These results indicate that both α and β adrenoceptors affect accommodation. Activation of α adrenoceptors increased the near point of accommodation and activation of β adrenoceptors decreased accommodative adaptation, which suggests that activation of adrenoceptors may modify parasympathetic activity; hence, affecting the state of accommodation.

Effects of topical application of adrenergic agents on refraction and accommodation

In an attempt to clarify the functional role of adrenergic receptors on accommodation, effects of various adrenergic agents on the state of accommodation were studied. Fifty-two emmetropic normal subjects (age: 19-28 y) participated in this study. We examined the effect of the alpha agonist phenylephrine hydrochloride (5%), the alpha 1 antagonist adrenergic bunazosin hydrochloride (0.1%), the beta antagonist timolol maleate (0.5%), the beta 2 antagonist betaxolal hydrochloride (0.5%), and the beta agonist isoproterenol hydrochloride (3%). Using an infrared optometer, the refraction, far point and near point of accommodation, resting point of accommodation (empty-field accommodation and dark focus of accommodation), and accommodative adaptation were measured before and after topical application of various adrenergic agents. Application of bunazosin slightly but significantly decreased the near point of accommodation. Isoproterenol evoked a hyperopic shift on the far point of accommodation. None of the agents had any effect on the resting point of accommodation. Accommodative adaptation was increased by timolol and betaxolol, and decreased by isoproterenol. We surmised that beta adrenergic agents exerted an indirect influence on the parasympathetic nervous system. The activation of beta receptors produced a hyperopic shift on the far point of accommodation and decreased accommodative adaptation, which suggests that activation of adrenergic receptors may reduce parasympathetic activity, hence affecting the state of accommodation.

Cardiovascular Regulation by ?-Arginine in the Brain of Rats Role of the Brain Renin-Angiotensin System and Nitric Oxide

The effect of brain L-arginine on arterial pressure was investigated by injecting L- or D-arginine into the cerebral ventricles of male Wistar rats that were anesthetized with urethane. Intracerebroventricular (I.C.V.) injection of 1 micromol L-arginine reduced the arterial pressure and the abdominal sympathetic nervous activity (SNA), whereas the injection of 10 micromol L-arginine induced a transient pressor response and reduced both the heart rate and SNA. Although I.C.V. injection of 1 micromol D-arginine had no effect on cardiovascular function or SNA, injection of 10 micromol of this enantiomer elicited a transient pressor response, similar to that induced by 10 micromol L-arginine, followed by a persistent increase in arterial pressure and a corresponding increase in SNA. I.C.V. pretreatment with the nitric oxide synthase inhibitor N(G)-monomethyl L-arginine abolished the vasodepressor response and reduced the inhibition of SNA induced by I.C.V. injection of 1 micromol L-arginine; such pretreatment increased the arterial pressure, heart rate, and SNA measured 30 min after I.C.V. injection of 10 micromol L-arginine. I.C.V. pretreatment with the angiotensin II type 1 receptor antagonist CV-11974 inhibited the pressor response to 10 micromol L-arginine and the first phase of the pressor response to 10 micromol D-arginine. Intravenous pretreatment with the alpha1-adrenoceptor blocker bunazosin hydrochloride abolished the pressor response to 10 micromol L-arginine and both phases of the pressor response to 10 micromol D-arginine. Brain L-arginine thus appears to exert pressor actions through stimulation of the brain renin-angiotensin system and peripheral SNA. However, these actions may be attenuated by L-arginine-derived nitric oxide.

Determination of α1-adrenoceptor antagonists in plasma by radioreceptor assay

A simple, rapid and sensitive radioreceptor assay (RRA) for the quantification of α 1-adrenoceptor antagonists such as prazosin in plasma is described. The method involves the use of an RRA based on [ 3H]prazosin displacement in rat cerebral cortical membranes. The method is reliable, with intra-assay and inter-assay RSDs ranging from 5.9 to 9.2%. The limit of detection is 0.2 (prazosin hydrochloride), 0.05 (tamsulosin hydrochloride) and 0.3 (bunazosin hydrochloride) pmol per assay. Using this method the plasma levels of prazosin hydrochloride were determined in beagle dogs administered orally 2.39 μmol kg −1 of this drug. The plasma levels of prazosin in beagle dogs are in good agreement with those obtained using a high-performance liquid chromatography (HPLC). This RRA proved to be applicable to the monitoring of plasma prazosin levels in patients with essential hypertension and/or benign prostatic hypertrophy receiving therapy with this drug with the therapeutic dosage schedule. Thus, the concentrations of α 1-adrenoceptor antagonists in plasma can be adequately monitored by RRA as well as by HPLC.

The effect of bunazosin on monocrotaline-induced pulmonary hypertension in rats.

In order to estimate the long-term hemodynamic and histologic effects of bunazosin hydrochloride on primary pulmonary hypertension (PPH), for which effective internal therapy has not yet been proposed, we produced subacute pulmonary hypertension in 6 week old Sprague-Dawley rats by injecting one dose of monocrotaline. Bunazosin (10 mg/kg) was administered intraperitoneally every day and bodyweight and hemodynamic parameters were measured. Right ventricle (RV) and left ventricle with septum (LV +S) were weight separately. Medial thickness of the small pulmonary artery was calculated. In the bunazosin group, the increase of right ventricular systolic pressure (RVSP) as pulmonary arterial systolic pressure and the ratio of RVSP to pulmonary flow were limited, without causing systemic hypotension, compared to the control group. Weight ratio of RV/(LV +S) had a tendency to be limited in the bunazosin group. As for medial thickness, there was no significant difference between the two groups. It may be concluded that bunazosin hydrochloride should be considered for clinical trials in treatment of PPH in humans.

本態性高血圧症の血圧の概日変動に対する塩酸Ｂｕｎａｚｏｓｉｎの効果についての検討

An open and non-randomized study was performed employing 10 patients (average age 54 years, 6 male and 4 female) with untreated essential hypertension to evaluate the efficacy on the circadian variation of blood pressure of bunazosin hydrochloride for more than 4 weeks. Mean values of systolic and diastolic blood pressure and heart rate for 48 hours every 30 minutes were obtained before and after the treatment using a noninvasive ambulatory monitor (model ABPM-630, Nippon Colin Inc., Japan). Each patient was administered bunazosin hydrochloride at a dose of 1 mg t. i. d. for more than 4 weeks. The data were analyzed with a conventional statistical method, hyperbaric index and the cosinor method during the day active and the night resting span, respectively. Systolic blood pressure (SBP) was significantly decreased from 160±6 to 152±7 mmHg (P<0.05) during the day active span, but this decrease was not significant during the night resting span. Diastolic blood pressure (DBP) also decreased significantly during the day active span, but not significantly during the night resting span. Hyperbaric indices and fractionated hyperbaric indices (hyperbaric index for every 4-hours) did not show a change in systolic and diastolic blood pressure or heart rate. MESOR (midline estimating statistic of rhythm) decreased significantly in SBP (p<0.05) and in DBP (p<0.01), however, circadian amplitude and acrophase did not change. 48-hour mean, means during the day active and during the night resting span, MESOR, amplitude and acrophase in heart rate did not show significant changes. In summary, bunazosin hydrochloride had antihypertensive effects on SBP and DBP especially during the day active span, but these were less effective on SBP and DBP during the night resting span and heart rate by this regimen.