Effects of diltiazem on in vitro cardiovascular actions of crude venom obtained from Okinawan box-jellyfish (Habu-kurage), Chiropsalmus quadrigatus.

The venom obtained from Okinawan box-jellyfish (Habu-kurage), Chiropsalmus quadrigatus, produced increases in contractions of isolated rat right atrial preparations in a concentration-dependent manner without changes in a spontaneous beating rate. These increases in contractions were significantly inhibited by diltiazem and did not show tachyphylaxis. The venom also produced increases in contractions of isolated rat aortic ring preparations (endothelium-intact) in a concentration-dependent fashion, which were reproducible with repeated application and were significantly inhibited by diltiazem or heating. These increases in vascular contractions were weakened in endothelium-denuded preparations, and almost abolished in a calcium-free medium. On the other hand, the venom at higher concentrations diminished contractions of both myocardial and vascular preparations and did not show reproducibility. These results suggest that the Habu-kurage venom is heat-labile and may increase contractions of cardiac muscle and aortic smooth muscle by increasing calcium influx into muscle cells, and that the venom at higher concentrations may produce dysfunction of muscle contractile systems due to calcium overload.

Effect of 1-week treatment with erythropoietin on the vascular endothelial function in anaesthetized rabbits.

Chronic administration of erythropoietin (EPO) is often associated with hypertension in animals and humans. The aim of this study was to estimate whether 1-week treatment with EPO can affect the vascular endothelial function. Rabbits were given with EPO (400 iu kg(-1) s.c.) or saline each other day for 1 week. Hypotensive responses to intravenously given acetylcholine (ACh), endothelium-independent nitric oxide donors (NOC7, nitroprusside and nitroglycerin) and prostaglandin I2 were tested before and after administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a specific nitric oxide synthase inhibitor, under pentobarbitone anaesthesia. Blood haemoglobin concentration in EPO group was significantly higher than that in control group, whereas baseline values of aortic pressure, heart rate and femoral vascular resistance were similar. The dose of ACh (172 ng kg(-1)) requiring for a 15 mmHg hypotension from the baseline in EPO group was apparently higher than that (55 ng kg(-1)) in control group. On the contrary, hypotensive responses to NOC7, nitroprusside, nitroglycerin and prostaglandin I2 were comparable between two groups. The extent of ACh-induced hypotension did not correlate with haemoglobin concentration. L-NAME significantly inhibited the ACh-induced vasodilating response in control group but did not in EPO group. In another set of rabbits, the same treatment with EPO also decreased vasodilating responses to carbachol, bradykinin and substance P besides ACh as compared with control group. These results indicate that 1-week treatment with EPO selectively attenuates depressor responses to endothelium-dependent vasodilators in anaesthetized rabbits, most likely due to inhibition of endothelial nitric oxide synthase.

Comparison of contractile responses relative to protein between isolated diabetic and non-diabetic rat aortae to KCl and alpha-adrenoceptor agonists in different extracellular calcium concentrations.

The influence of extracellular Ca2+ concentration on contractile responses of aortae isolated from diabetic rats to KCl and alpha-adrenoceptor agonists was compared with that of non-diabetic rat aortae. Diabetic rats 6 weeks after administration of streptozotocin showed significantly lower body weight and higher plasma glucose concentration, but the protein content per each aortic ring preparation was not significantly different from that of non-diabetic preparation. Both diabetic and non-diabetic aortae showed concentration-dependent contractile responses to norepinephrine, which were concentration-dependently inhibited by prazosin. On the other hand, clonidine induced small contractions in both aortae, which tended to be more inhibited by prazosin than yohimbine. In non-diabetic aortae, the contractile responses to KCl, norepinephrine, methoxamine and clonidine were significantly greater with 2.5 mmol/l of extracellular Ca2+ than 1.25 mmol/l. In diabetic aortae, however, the contractile responses were not significantly influenced by changes in extracellular Ca2+ concentration. Additionally, the contractile responses to each agonist were markedly greater in non-diabetic aortae than diabetic ones. The present results indicate that the contractions of diabetic vasculature do not respond to changes in extracellular Ca2+ concentration, suggesting that there may be some impairment of Ca2+ related mechanisms.

Beneficial hemodynamic effects of nicorandil in a canine model of acute congestive heart failure: comparison with nitroglycerin and cromakalim.

Comparative hemodynamic effects of nicorandil (NCR), nitroglycerin (NTG) and cromakalim (CRM) were examined in a canine model of acute congestive heart failure (CHF). CHF was produced by injections of saponin into coronary arteries of anesthetized dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF), left ventricular dP/dt and myocardial segment shortening (SS) markedly decreased, while the left ventricular end-diastolic pressure (LVEDP), the right atrial pressure (RAP) and the systemic vascular resistance (SVR) increased. NCR (n = 6), NTG (n = 6) and CRM (n = 8), which were administered i.v. after production of CHF, caused a comparable reduction in LVEDP. NCR and CRM profoundly increased AoF and SS but NTG did only slightly. On the other hand, NTG and NCR but not CRM significantly reduced RAP. Intracoronary NCR (n = 8) exerted no or similar effects on SS as well as systemic hemodynamic indices to those observed with i.v. NCR despite distinct coronary vasodilation. These results indicate that NCR may exert beneficial hemodynamic effects in an experimental CHF mainly due to lessening both afterload and preload rather than the coronary vasodilating effect.

Role of high glycogen in underperfused diabetic rat hearts with added norepinephrine.

The relationship between cardiac dysfunction and glycogen level and/or duration of diabetes was examined during underperfusion (2 ml/min/g heart weight) with 10(-6)M norepinephrine (NE) in isolated 1- and 6-week streptozotocin-diabetic rat (diabetes mellitus, DM) hearts and non-DM hearts. Glycogen levels in non-DM and 1- and 6-week DM hearts were 85, 120, and 206 mumol/g dry weight, respectively, in the subendocardium. About 13 min after the start of underperfusion with NE, the diastolic tension in 1-week DM hearts began to increase when the glycogen level had decreased to half; in 6-week DM hearts, glycogen decreased more markedly without greater lactate accumulation, but these glycogen levels were still higher (104 mumol/g dry weight) than those in 1-week DM hearts and the diastolic tension did not increase. About 17 min after the onset of underperfusion, the glycogen decreased to the 13-min level of 1-week DM hearts (64 mumol/g dry weight) and the diastolic tension began to increase. Until 20 min after the onset of underperfusion, the injury was less in 6-week than in 1-week DM hearts. However, after 60-min underperfusion with NE, when the glycogen level was markedly low in both groups ( < 20 mumol/g dry weight), diastolic tension was increased twice as much in 6-week DM as in 1-week DM hearts and was related to the decreased subendocardial ATP level. The results indicate that the markedly high glycogen content in diabetic hearts probably helps delay the start of the increase in left ventricular (LV) stiffness during underperfusion with NE. Ultimately, however, the degree of the injury depends on the duration, i.e., the severity, of the diabetes.

Inhibitory effect of vapiprost on contractile responses of isolated dog renal arteries to thromboxane A2 analogue, U46619.

1. Cumulative administrations of U46619, a thromboxane A2 analogue, and prostaglandin (PG) F2 alpha produced concentration-dependent contractions of isolated dog renal arterial preparations, which were significantly and concentration-dependently inhibited by vapiprost. 2. A bolus administration of U46619 or PGF2 alpha produced sustained contracture of these preparations, which was concentration-dependently relaxed by cumulative vapiprost. 3. Results indicate that vapiprost inhibits U46619- and PGF2 alpha-induced dog renal arterial contractions through antagonism for so-called TP receptors.

Effects of pilsicainide on systemic hemodynamics and cardiac function of anesthetized dogs.

The effects of pilsicainide, propafenone and flecainide on systemic hemodynamics and cardiac function were compared in anesthetized open-chest dogs. Pilsicainide, propafenone and flecainide given intravenously at 1 and 3 mg/kg produced dose-dependent decreases in the mean aortic pressure. The heart rate was decreased by pilsicainide and flecainide, but not by propafenone. The three drugs increased the left ventricular end-diastolic pressure and reduced the first derivative of left ventricular pressure and myocardial oxygen consumption. Pilsicainide decreased aortic, vertebral, coronary and renal blood flows in a dose-dependent manner at 1 and 3 mg/kg. Propafenone increased aortic and vertebral blood flows at 1 mg/kg and decreased coronary and renal blood flows at 3 mg/kg. Flecainide did not significantly change blood flow, except for an increase in the aortic blood flow with 3 mg/kg. The total peripheral, vertebral, coronary and renal vascular resistances were increased by pilsicainide, but not by flecainide. Propafenone decreased total peripheral and vertebral vascular resistances, but hardly affected the coronary and renal vascular resistances. The stroke volume was decreased by 1 and 3 mg/kg pilsicainide in a dose-dependent manner, and increased by 1 and 3 mg/kg propafenone, but not significantly changed by 1 or 3 mg/kg flecainide. The stroke work index was decreased by 3 mg/kg pilsicainide and 3 mg/kg flecainide. The effects of pilsicainide correlated with the changes in its plasma concentration with time. The results indicate that pilsicainide has a negative inotropic activity similar to that of propafenone and flecainide. Pilsicainide and flecainide show almost the same effects with a slightly different efficacy, while propafenone exerts different effects upon some cardiovascular functions.

Effects of the new thromboxane A2 antagonist vapiprost on isolated canine blood vessels.

Effects of the new thromboxane A2 antagonist vapiprost (SN-309, GR-32191B, CAS 85505-64-2) on isolated canine blood vessels were investigated. U46619 ((15S)-hydroxy-11a, 9a-(epoxymethano) prosta-5Z, 13E-dienoic acid) 10(-10)-10(-6) mol/l, a thromboxane A2 analogue, produced concentration-dependent contractions of oblong or ring preparations isolated from basilar, coronary, mesenteric and femoral arteries. Vapiprost 10(-8) and 10(-7) mol/l significantly and concentration-dependently shifted the concentration-contraction curves for U46619 of these arteries to the right. The pA2 values were 8.80 +/- 0.09 in basilar arteries, 8.67 +/- 0.12 in coronary arteries, 8.86 +/- 0.05 in mesenteric arteries and 9.01 +/- 0.07 in femoral arteries. On the other hand, oblong or ring preparations of basilar, coronary, mesenteric and femoral arteries showed sustained contractile responses to KCl 3 x 10(-2) mol/l, U46619 10(-7) mol/l or prostaglandin (PG) F2 alpha 10(-5) mol/l. Norepinephrine (NE) 3 x 10(-5) mol/l also produced sustained contractions in mesenteric and femoral arterial preparations, but not in basilar and coronary arterial preparations. Vapiprost 10(-10)-3 x 10(-6) mol/l relaxed these four arterial preparations constricted with U46619 10(-7) mol/l and PGF 2 alpha 10(-5) mol/l in a concentration-dependent fashion, but hardly affected them constricted with KCl 3 x 10(-2) mol/l. NE 3 x 10(-5) mol/l-induced contractures of mesenteric and femoral arterial preparations were not influenced by any concentrations of vapiprost. Results indicate that vapiprost has an antagonistic action on a so-called TP-receptor and/or a vasoconstrictive prostaglandin(s)-receptor and thus produces vasorelaxation.

Effects of denopamine with or without diltiazem on the ischemic heart of anesthetized dogs.

Effects of denopamine with or without diltiazem on the ischemic heart were investigated in anesthetized open-chest dogs. Partial occlusion of the left circumflex coronary artery (LCX) produced significant decreases in LCX flow and regional myocardial segment shortening rate (%SS) in the LCX-perfused area, and a significant increase in left ventricular enddiastolic pressure (LVEDP). Heart rate (HR) and mean aortic pressure (mAoP) were not altered, but aortic flow (AoF), positive first derivative of left ventricular pressure ((+)LVdP/dt), stroke volume (SV), stroke work index (SWI) and double product showed a tendency to decrease. Total peripheral vascular resistance (TPR) tended to increase. During coronary stenosis, saline infusion (vehicle group) did not change any parameter, but diltiazem infusion (diltiazem group) decreased HR, mAoP, TPR and double product and increased SV and SWI. Under these conditions, denopamine infusion produced increases in HR, mAoP, AoF, (+)LVdP/dt and double product and decreases in LVEDP and TPR in both groups. %SS in the left anterior descending coronary artery-perfused area was increased, but %SS in the LCX-perfused area was slightly decreased in both groups. SV and SWI were decreased by denopamine infusion in the vehicle group, while they were increased in the diltiazem group. Differences in changes in SV and SWI between the groups were statistically significant. Results suggest that combined treatment of denopamine and diltiazem may exert an advantage in alleviation of heart failure due to coronary stenosis.

Cardiovascular effects of Acanthaster planci venom in the rat: possible involvement of PAF in its hypotensive effect.

Cardiovascular effects of the crowns-of-thorns starfish (Acanthaster planci) venom were examined in rats. The crude venom extracted from the spines of A. planci caused systemic hypotension associated with an increase in heart rate and a decrease in renal cortical blood flow when given i.v. The hypotensive effect of the venom was not inhibited by pretreatment with atropine, indomethacin or aprotinin, but was significantly inhibited by SRI 63-441, a platelet activating factor (PAF) antagonist. The venom caused dose-dependent vasorelaxation of the isolated rat aortic ring preparation precontracted by noradrenaline, an effect which was significantly attenuated by pretreatment with SRI 63-441, methylene blue or parabromophenacyl bromide. Denudation of the endothelium also diminished the vasorelaxing effect of the venom. Both the vasorelaxing and the hypotensive effects showed tachyphylaxis. These results suggest the release of PAF or a PAF-like substance from the endothelium by the venom.

Possibilities of the tolerance development to nipradilol and of the measurement of vascular glutathione content in isolated rat aorta.

1. Nipradilol produced concentration-dependent relaxations of isolated rat aorta ring preparations under the contracture induced by norepinephrine or KCl, which were not significantly influenced by the previous incubation with nipradilol but significantly depressed by methylene blue. 2. The previous incubation with nipradilol did not influence the relaxant responses to nitroglycerin. 3. Five different methods for measurement of vascular glutathione content did not give the satisfiable results on the detected value of glutathione content in isolated rat aorta tissues. 4. Results indicate that nipradilol will not develop the tolerance to nipradilol itself and nitroglycerin.

Pharmacological properties of 5-[(6,7,8-trimethoxy-4-quinazolinyl) amino]-1-pentanyl nitrate maleate in cardiovascular system.

Effects of 5-[6,7,8-trimethoxy-4-quinazolinyl)amino]-1-pentanyl nitrate maleate (KT-1, CAS 47487-05-8), whose chemical structure has both a prazosin and a nitrate moiety, on cardiovascular system were investigated in in vivo and in vitro experiments. KT-1 i.v. decreased aortic pressure, renal blood flow, left ventricular enddiastolic pressure and resistances of total peripheral, vertebral, coronary and renal vasculatures and increased aortic blood flow, vertebral blood flow, coronary blood flow, peak positive left ventricular dP/dt and heart rate in anesthetized open-chest dogs. These cardiovascular effects of KT-1 were similar to those of glyceryl trinitrate (nitroglycerin, GTN). Nitrate-deleted KT-1 from its chemical structure (denitro KT-1) equimolar to KT-1 produced no marked changes in these cardiovascular parameters, but 3 or 10 times large doses of denitro KT-1 showed relatively long persisting vasodilator effects. In isolated dog coronary artery preparations contracted with KCl, the order of relaxant potency was GTN greater than KT-1 greater than denitro KT-1. In isolated dog mesenteric artery preparations, phenylephrine produced concentration-dependent contractions which were significantly inhibited by prazosin and KT-1 but not by denitro KT-1. In anesthetized open-chest dogs, phenylephrine produced pressor responses which were significantly inhibited by KT-1 but not by GTN or denitro KT-1. In isolated rat thoracic aorta strips, in contrast to GTN, KT-1 hardly developed a tachyphylaxis. Thus, KT-1 showed cardiovascular effects similar to those of both nitrates and a1-adrenoceptor blocking agents with no development of a tachyphylaxis.

Regional vasodilating effects of spirapril diacid and enalapril diacid in anesthetized dogs.

The acute regional hemodynamic effects of spirapril diacid, a novel nonsulfhydryl angiotensin-converting enzyme inhibitor, and enalapril diacid at an equidepressor dose were examined in anesthetized dogs by simultaneously measuring renal, coronary, vertebral arterial and aortic blood flow. Spirapril diacid (30 micrograms/kg, i.v.) lowered aortic pressure and increased aortic and renal blood flow associated with no marked change in heart rate, myocardial contractility, vertebral and coronary blood flow in a similar manner to enalapril diacid (30 micrograms/kg, i.v.). Both inhibitors thus produced an increase in stroke volume and a decrease of the rate-pressure product. The decrease of renal vascular resistance after administration of both agents was greater than that in vertebral and coronary vascular beds. A relatively more prolonged renal vasodilatation and a shortened coronary vasodilatation were seen with spirapril diacid as compared with enalapril diacid, despite practically identical reductions in total peripheral resistance. Each of the drugs markedly inhibited the pressor and renal vasoconstrictor responses to angiotensin I. These results indicate that the two inhibitors exhibit a similar profile of regional differences in vasodilatory effects, although they might display different durations of regional vasodilatation.

Effect of polyoxyethylene-modified superoxide dismutase on recovery of myocardial dysfunction after coronary stenosis in dogs.

The effects of superoxide dismutase modified with polyoxyethylene (SOD-POE) on impairment of myocardial segment shortening (SS) during coronary stenosis plus pacing-induced tachycardia (CSPT) and the recovery after reperfusion was examined in anesthetized dogs. SOD-POE or saline was administered i.v. 30 min before reperfusion. Changes in hemodynamic variables and SS by CSPT were similar in both groups. However, the SOD-POE group showed improved recovery of SS compared with the control group. Results indicate that oxygen-derived free radicals may partially be involved in the genesis of myocardial dysfunction after CSPT-induced regional ischemia.

Investigation on the effect of dipyridamole and papaverine on regional blood flow and cardiac hemodynamics in anesthetized dogs.

Vasodilating effects of dipyridamole were compared with those of papaverine in anesthetized open-chest dogs. Dipyridamole i.v. produced a significant fall in aortic blood pressure and significant increases in aortic and coronary blood flows. Vertebral blood flow did not alter, but renal blood flow was transiently decreased. Left ventricular dP/dt, heart rate and left ventricular enddiastolic pressure were hardly affected by dipyridamole. Papaverine i.v. significantly increased aortic, vertebral and coronary blood flows, left ventricular dP/dt and heart rate and significantly decreased aortic blood pressure and left ventricular enddiastolic pressure. Renal blood flow was instantly decreased by papaverine. Percent change in each vascular resistance showed decreases in total peripheral, vertebral and coronary vascular resistances in response to both drugs, and the decrease in coronary vascular resistance was the most remarkable. Renal vascular resistance was increased by dipyridamole, while it was decreased by papaverine. Percent change in double product (heart rate x systolic arterial blood pressure) showed a monophasic decrease pattern with dipyridamole and a biphasic pattern with an initial, transient decrease followed by an increase with papaverine. The present results indicate that dipyridamole and papaverine produce marked coronary vasodilatation, and that papaverine is different from dipyridamole in cardiotonic properties.

Effects of atenolol and some other beta-adrenoceptor blocking agents on norepinephrine-induced responses in isolated and perfused rat hearts.

The effects of atenolol and another three beta-adrenoceptor blocking agents on norepinephrine (NE)-induced cardiac responses were examined in isolated and perfused rat hearts following a Langendorff method. Bolus injection of atenolol did not show significant inhibitory effects on NE-induced increases in myocardial contractile force (MCF) and heart rate. Bolus injections of metoprolol and timolol were also ineffective for inhibiting NE-responses. However, both bolus injection and infusion of propranolol or infusion of atenolol, metoprolol and timolol all significantly inhibited NE-responses. On sustained increase in MCF induced by infusion of NE, the inhibitory effect of atenolol was transient, while that of propranolol was continuous. From these results, it is concluded that atenolol displays a different time course of action on NE-induced cardiac responses by bolus injection or infusion because of its pharmacological properties, which may be due to its low lipophilicity.

Comparative effects of the calcium antagonist isradipine and some other dihydropyridine derivatives on regional blood flow in anesthetized open-chest dogs.

The effects of isradipine (PN 200-110), isopropyl 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-5-methoxycarbonyl-2,6-dim ethyl-3- pyridinecarboxylate, on some cardiovascular parameters and regional blood flow were compared with those of other dihydropyridine derivatives in anesthetized open-chest dogs. Intravenous (i.v.) administrations of isradipine 3 and 10 micrograms/kg, nifedipine 10 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg, decreased aortic blood pressure and increased aortic (AoF), vertebral (VBF) and coronary blood flow (CBF), but did not affect heart rate and left ventricular end-diastolic pressure. Renal blood flow was reduced by isradipine 10 micrograms/kg and nifedipine 10 micrograms/kg, but was not influenced by isradipine 3 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg. Left ventricular dP/dt was increased by isradipine 3 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg, but remained essentially unchanged following isradipine 10 micrograms/kg and nifedipine 10 micrograms/kg. The increase in AoF, VBF and CBF lasted 5-9 min following nifedipine 10 micrograms/kg or nicardipine 10 micrograms/kg, 17-30 min following nifedipine 10 micrograms/kg or nicardipine 10 micrograms/kg, 17-30 min following nisoldipine 10 micrograms/kg, and 16-44 min following isradipine 3 micrograms/kg i.v., but persisted for at least 60 min following isradipine 10 micrograms/kg. Under the experimental conditions and at the doses used in this study, all 4 drugs reduced total peripheral resistance as well as resistance in the vertebral, coronary and renal vascular beds. The results suggest that isradipine exerts cardiovascular effects similar to other calcium antagonists of the dihydropyridine group, but possesses a longer duration of action and shows a greater specificity in reducing coronary vascular resistance than nifedipine, nicardipine and nisoldipine.

An analysis of the depressant effect of indomethacin on contractions of isolated and perfused rat hearts.

The depressant effect of indomethacin on contractions of isolated rat hearts was investigated under a constant heart rate. Ca2+ produced dose-dependent increases in myocardial contractile force and coronary perfusion pressure. Indomethacin-infusion significantly decreased myocardial contractile force and depressed increases in myocardial contractile force by Ca2+, but never affected both coronary perfusion pressure and increases in coronary perfusion pressure by Ca2+. Results suggest that indomethacin will depress myocardial contractile force with no involvement of any calcium antagonism.

Comparison of vasodilating effects of nisoldipine and nifedipine in anesthetized open-chest dogs.

Hemodynamic effects of nisoldipine (Bay k 5552) were compared with those of nifedipine in anesthetized open-chest dogs. Both nisoldipine and nifedipine produced a fall in aortic pressure and increases in aortic, vertebral and coronary blood flows. After administration of nisoldipine, renal blood flow, heart rate and left ventricular enddiastolic pressure were not changed, but left ventricular dP/dt was increased. After administration of nifedipine, renal blood flow and left ventricular dP/dt were decreased, and left ventricular enddiastolic pressure was elevated. Heart rate was hardly changed. Durations of increases in aortic, vertebral and coronary blood flows were about 3 times longer after nisoldipine than after nifedipine. Percent decrease in coronary vascular resistance was greater and percent decrease in renal vascular resistance was smaller than that in total peripheral vascular resistance with both nisoldipine and nifedipine. Results indicate that nisoldipine and nifedipine produce marked coronary vasoldilation and the vasodilating effect of nisoldipine lasts longer than that of nifedipine.

Acute effects of bunazosin on aortic, vertebral, coronary and renal blood flows of anesthetized dogs.

Effects of 4-amino-2-(4-butyrylhexahydro-1H-1,4-diazepin-1-yl)-6,7-dime thoxy-quinazoline (bunazosin, E-643, Detantol) on aortic, vertebral, coronary and renal blood flows were investigated in anesthetized open-chest dogs. Bunazosin 1, 10 and 100 micrograms/kg i.v. dose-dependently decreased aortic blood pressure (AoP) and inhibited the increase in AoP by phenylephrine 5 micrograms/kg i.v. However, the increase in AoP by norepinephrine 0.5 microgram/kg i.v. remained even after bunazosin 100 micrograms/kg i.v. and was almost undetectable after additional administration of yohimbine 1000 micrograms/kg i.v. A hypotension by bunazosin persisted more than 15 min, but dose-dependent increases in heart rate (HR) induced by bunazosin 1, 10 and 100 micrograms/kg i.v. restored within 2 min. Bunazosin 100 micrograms/kg i.v. significantly but transiently increased aortic blood flow and decreased renal blood flow. Vertebral and coronary blood flows were not significantly changed. Left ventricular dP/dt was transiently increased. Calculated total peripheral vascular resistance and coronary vascular resistance were transiently but significantly decreased. No significant changes were observed in both vertebral vascular resistance and renal vascular resistance. The results indicate that bunazosin maintains the blood flows to brain, heart and kidney, and is continuously lowering AoP without significant changes in HR.