Central mechanisms of action involved in cocaine-induced tachycardia

The present study was designed to determine the central effects of cocaine on heart rate and blood pressure in Wistar Kyoto rats (WKY) and to evaluate mechanisms involved in the response. Cocaine (0.025-4 mg/kg) was administered to unanesthetized, unrestrained rats via a cannula placed into the lateral ventricle. Procaine (0.1 and 4 mg/kg) was also administered centrally. Cocaine did not significantly alter blood pressure at doses of 0.025, 0.1, or 0.5 mg/kg, icv. Only the highest dose, 4 mg/kg, icv produced a significant pressor response. Cocaine produced significant dose-dependent tachycardia, with the maximum increase in heart rate occurring within 5 min. Procaine (4 mg/kg, icv) produced tachycardia, but the effect was significantly less than that produced by cocaine (4 mg/kg, icv). Cocaine also produced tachycardia at a dose of 0.1 mg/kg, but procaine did not significantly alter heart rate at the same dose. Central phentolamine pretreatment (0.1 mg/kg, icv) significantly attenuated the increase in heart rate produced by cocaine. These results indicate that the centrally mediated tachycardia produced by cocaine is partly due to its local anesthetic activity and to indirect stimulation of alpha receptors.     

Effects of alpha-1 adrenergic receptor antagonist, terazosin, on cardiovascular functions in anaesthetised dogs

Initially a dose-response curve of phenylephrine was constructed at dose strengths of 1-16 microg/kg in a cumulative manner. Phenylephrine caused a significant rise in the mean arterial pressure, left ventricular systolic pressure, left ventricular contractility, stroke volume and a significant decline in the heart rate. Terazosin was administered in three selected doses of 10, 100 and 300 microg/kg. Following each dose of terazosin, dose-response curve of phenylephrine was constructed. Terazosin, per se, decreased the basal mean arterial pressure, left ventricular systolic pressure, left ventricular contractility and stroke volume significantly in a dose dependent manner with an increase in the heart rate with no significant change in the cardiac output. The baroreflex sensitivity at all the three doses remained unchanged. In conclusion, the present findings support the view that terazosin reduces the blood pressure in a physiologically more favorable manner by maintaining the neural integrity of the cardiovascular system.     

Drug-induced arterial pressure elevation is associated with arousal from NREM sleep in normal volunteers.

Abrupt changes in arterial pressure produce arousal in sleeping animals. To determine whether arterial pressure elevations can cause arousal from sleep in humans, we studied five healthy individuals without sleep complaints or cardiac abnormalities. Monitoring included electroencephalogram, electrooculogram, and electromyogram to determine stage sleep; finger cuff to measure arterial pressure; and electrocardiogram to measure heart rate. We administered intravenous bolus doses of either phenylephrine or saline after performing a dose-response curve to establish the amount of phenylephrine that produced a 20-mmHg increase in mean arterial pressure. Ten boluses of phenylephrine and ten boluses of saline were then administered in random order during stable non-rapid-eye-movement sleep. An observer blinded to the order of drug administration identified arousals using a standard definition. Arousals were five times more likely to occur after phenylephrine than after saline (58 vs. 12%; P = 0.0071). Phenylephrine administration produced heart rate slowing, indicative of baroreflex stimulation. We conclude that pharmacologically induced arterial pressure elevation is associated with arousal from sleep in normal volunteers.     

Refined anaesthesia for implantation of engineered experimental aortic valves in the pulmonary artery using a right heart bypass in sheep

The feasibility of an anaesthetic protocol developed for surgery during right heart bypass in sheep is reported. Seven female Suffolk sheep, weighing 25-35 kg, were selected for the study. Premedication consisted of midazolam and methadone (both 0.1 mg kg(-1) intravenously). Anaesthesia was induced with propofol (2-4 mg kg(-1)) and maintained with isoflurane in oxygen and continuous rate infusions of propofol (5-7 mg kg(-1 )h(-1)) and fentanyl (5 microg kg(-1) bolus, 5 microg kg(-1) h(-1)). Cisatracurium (0.2 mg kg(-1)) provided muscle relaxation. A standard roller pump was used for the extracorporeal circulation. Drugs administered to maintain blood pressure and heart rate within acceptable levels included phenylephrine (3-4 microg kg(-1)), ephedrine (0.1-0.2 mg kg(-1)), nitroglycerine (50-150 microg kg(-1) h(-1)) and metoprolol succinate (30-80 microg kg(-1)). Electrolytes were infused as needed. Postoperative analgesia was provided by an intercostal block (15 mL 0.5% bupivacaine + epinephrine), carprofen (4 mg kg(-1)) and an opioid (methadone 0.1 mg kg(-1) or buprenorphine 0.01 mg kg(-1)). One sheep became hypoxic during the bypass (PaO(2) 47.7 mmHg). Irregularities of the electrocardiogram were observed during manipulation of the heart in all animals. During the initial phase of the bypass, blood pressure decreased in all sheep, accompanied by dilatation of the heart and large intrathoracic veins in five sheep. With appropriate treatment, blood pressure was restored and easily maintained until the end of the bypass. Weaning from the bypass, using an infusion of nitrates, was smooth. One sheep required a blood transfusion because of severe blood loss and another sheep died postoperatively from respiratory complications. Minor irregularities of the electrocardiogram observed during manipulation of the heart were not life threatening and required no treatment. Decreases in blood pressure at the beginning of the bypass can be expected and require treatment. Nitrates are useful in avoiding volume overload during weaning. The anaesthetic protocol is acceptable for surgery under right heart bypass in sheep.     

Effects of high-frequency jet ventilation on arterial baroreflex regulation of heart rate

Fifteen anesthetized mechanically ventilated patients recovering from multiple trauma were studied to compare the effects of high-frequency jet ventilation (HFJV) and continuous positive-pressure ventilation (CPPV) on arterial baroreflex regulation of heart rate. Systolic arterial pressure and right atrial pressure were measured using indwelling catheters. Electrocardiogram (ECG) and mean airway pressure were continuously monitored. Lung volumes were measured using two linear differential transformers mounted on thoracic and abdominal belts. Baroreflex testing was performed by sequential intravenous bolus injections of phenylephrine (200 micrograms) and nitroglycerin (200 micrograms) to raise or lower systolic arterial pressure by 20-30 Torr. Baroreflex regulation of heart rate was expressed as the slope of the regression line between R-R interval of the ECG and systolic arterial pressure. In each mode of ventilation the ventilatory settings were chosen to control mean airway pressure and arterial PCO2 (PaCO2). In HFJV a tidal volume of 159 +/- 61 ml was administered at a frequency of 320 +/- 104 breaths/min, whereas in CPPV a tidal volume of 702 +/- 201 ml was administered at a frequency of 13 +/- 2 breaths/min. Control values of systolic arterial pressure, R-R interval, mean pulmonary volume above apneic functional residual capacity, end-expiratory pulmonary volume, right atrial pressure, mean airway pressure, PaCO2, pH, PaO2, and temperature before injection of phenylephrine or nitroglycerin were comparable in HFJV and CPPV. Baroreflex regulation of heart rate after nitroglycerin injection was significantly higher in HFJV (4.1 +/- 2.8 ms/Torr) than in CPPV (1.96 +/- 1.23 ms/Torr).(ABSTRACT TRUNCATED AT 250 WORDS)     

Phenylephrine-induced elevations in arterial blood pressure are attenuated in heat-stressed humans

To test the hypothesis that phenylephrine-induced elevations in blood pressure are attenuated in heat-stressed humans, blood pressure was elevated via steady-state infusion of three doses of phenylephrine HCl in 10 healthy subjects in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature by ~0.5 degrees C, muscle sympathetic nerve activity (MSNA), heart rate, and cardiac output and decreased total peripheral vascular resistance (TPR; all P < 0.005) but did not change mean arterial blood pressure (MAP; P > 0.05). At the highest dose of phenylephrine, the increase in MAP and TPR from predrug baselines was significantly attenuated during the heat stress [DeltaMAP 8.4 +/- 1.2 mmHg; DeltaTPR 0.96 +/- 0.85 peripheral resistance units (PRU)] compared with normothermia (DeltaMAP 15.4 +/- 1.4 mmHg, DeltaTPR 7.13 +/- 1.18 PRU; all P < 0.001). The sensitivity of baroreflex control of MSNA and heart rate, expressed as the slope of the relationship between MSNA and diastolic blood pressure, as well as the slope of the relationship between heart rate and systolic blood pressure, respectively, was similar between thermal conditions (each P > 0.05). These data suggest that phenylephrine-induced elevations in MAP are attenuated in heat-stressed humans without affecting baroreflex control of MSNA or heart rate.     

Cerebellar fastigial nuclei activity during blood pressure challenges.

The cerebellar fastigial nuclei (FN) assist in regulating compensatory responses to large blood pressure changes and show structural injury and functional impairment to cardiovascular challenges in syndromes with sleep-disordered breathing. The patterned time course of FN responses to elevation or lowering of blood pressure and location of responsive regions within the nuclei are unclear. We evaluated FN neural activity in six anesthetized rats using optical imaging procedures during elevation and lowering of arterial pressure by phenylephrine and nitroprusside, respectively. Hypertension diminished optical correlates of FN neural activity, while measures of activity increased to hypotension, with peak neural responses occurring 5-10 s later than peak blood pressure changes. Blood pressure responses were followed by heart rate changes, and peak respiratory rates developed even later, in close temporal proximity to FN activity patterns. Although overall topographical response trends were similar, regional patterns of altered neural activity appeared to both hypertension and hypotension. The extent of neural change was greater during recovery from hypertension than for hypotension at high-dose levels. Blood pressure levels saturated with increasing phenylephrine doses, while FN activity continued to decline. No saturation appeared in heart or respiratory rate trends. The findings suggest that the FN compensate for large blood pressure changes by sympathoexcitatory and inhibitory processes, which accompany late-developing somatic or respiratory adjustments.     

Pharmacological effects of 1,2,3,5,6,10b-hexahydropyrido[2,3g]indolizine, a bridged-nicotine analog

The racemate of a bridged-nicotine (BN) analog was synthesized and resolved into its enantiomers for pharmacological comparisons to (+)- and (-)-nicotine. The EC50 values for (-)- and (+)-nicotine and (-)- and (+)-BN were 4, 170, 53 and 400 microM, respectively, for producing contractions of guinea-pig ilea. (-)-Nicotine was an effective antinociceptive agent in the mouse tail-flick procedure at i.v. doses of 0.1-0.3 mg/kg, whereas the isomers of BN failed to alter tail-flick response in doses up to 5 mg/kg. (-)-Nicotine (0.01-0.3 mg/kg, i.v.) increased blood pressure and decreased heart rate in anesthetized rats. Neither (+)- nor (-)-BN altered blood pressure and heart rate in rats in this dosage range. At doses of 3-100 mg/kg, (+)-BN produced an increase in blood pressure without changing heart rate, while (-)-BN decreased both blood pressure and heart rate. Bridging the pyrrolidine and pyridine rings decreased biologic activity and did not result in stereoselectivity greater than that observed with (+)- and (-)-nicotine. It appears that there may be subpopulations of nicotine receptors to which the isomers of BN do not interact.     

Effects of Salbutamol and Isoprenaline Phenylephrine in Reversible Airways Obstruction

Ventolin (salbutamol) and Medihaler-Duo (isoprenaline/phenylephrine combination) standard pressurized inhalers were used to administer doses of two or six “puffs” to 16 patients with known reversible airways obstruction. The doses were administered in random order over two days. Both the Ventolin and Medihaler-Duo inhalers substantially increased FEV₁, but in the doses used salbutamol was more effective than isoprenaline/phenylephrine (P < 0·01). There was no significant difference between two and six puffs of salbutamol, though there seemed to be an advantage of six puffs of isoprenaline/phenylephrine over two puffs (P < 0·05). Adrenaline (1/1,000) 0·5 ml and atropine 0·6 mg produced similar increases in FEV₁ to those produced by salbutamol.The Pao₂ fell more than 5 mm Hg in three patients after salbutamol and in three after isoprenaline/phenylephrine. There was no significant fall in mean Pao₂ in any of the treatment groups. It is concluded that the Ventolin inhalant, administered in the conventional dose of two puffs, is as effective a bronchodilator as subcutaneous adrenaline and atropine, is more effective than the Medihaler-Duo, and is without detectable side effects.     

Combined use of dopamine and prostaglandin A1 in patients with acute renal failure and hepatorenal syndrome.

Dopamine and prostaglandin A1 were infused intravenously in 4 patients with the hepatorenal syndrome, in 1 patient with acute tubular necrosis, and 1 patient with cortical necrosis. Large doses of prostaglandin A1 decreased arterial blood pressure preventing increase in dosage; in contrast, high doses of dopamine elevated blood pressure. When the two drugs were administered conjointly, much larger doses of each agent could be administered without change in arterial blood pressure. Significant improvement of renal function was not observed in any of these critically ill patients during or within 24 hours after dopamine and prostaglandin A1 administration. This study demonstrated that extremely large doses of these vasodilating agents can be safely administered conjointly.     

Cardiovascular responses to catecholamines at 12 degrees C in the American bullfrog (Rana catesbeiana)

The effects of epinephrine, norepinephrine, phenylephrine, and isoproterenol on blood pressure and heart rate were studied in cannulated American bullfrogs, Rana catesbeiana. The bullfrogs were chronically cannulated with a T cannula in the right sciatic artery. In warm-acclimated (22 degrees C) bullfrogs, preinjection mean systemic arterial pressure (SAP) prior to experimental treatment was 13.1 +/- 0.7 mm Hg. Preinjection heart rate was 34.8 +/- 1.8 beats per minute. These parameters were lower in cold-acclimated (12 degrees C) bullfrogs. Cold-acclimated animals had mean SAP values of 8.2 +/- 0.3 mm Hg, and heart rate was 11.1 +/- 1.1 beats per minute. Epinephrine, norepinephrine, and phenylephrine increased blood pressure to an equivalent degree in warm- and cold-acclimated animals. Dose-related decreases in heart rate in response to these catecholamines were observed in warm- but not in cold-acclimated bullfrogs. Warm-acclimated animals were more responsive to isoproterenol from 0.03 micrograms/kg body weight (bw) to 10 micrograms/kg bw than were cold-acclimated animals. The response to isoproterenol was effectively blocked by propranolol (5 mg/kg bw) in both warm- and cold-acclimated animals. Propranolol alone decreased mean SAP in both warm- and cold-acclimated animals, suggesting blockade of endogenous sympathetic activity. Beta receptor response thus appears diminished, but not absent at 12 degrees C. However, the alpha receptors responsible for elevation of blood pressure equally responsive at 12 degrees and 22 degrees C.     

不同剂量胺碘酮联合氯沙坦治疗阵发性房颤患者复律后的窦性心律维持效果

目的:研究不同剂量胺碘酮联合氯沙坦治疗阵发性房颤患者复律后的窦性心律维持效果。方法:选取2013年1月到2014年1月我院收治的阵发性房颤患者130例,按照随机数字表法将患者分为A组和B组,每组65例,两组均给予氯沙坦治疗,A组给予胺碘酮600 mg/d,1-2周后改用200 mg/d维持1年;B组给予胺碘酮600 mg/d,1-2周后改用200 mg/d,1个月后改为100mg/d维持1年,比较两组治疗前后转复维持有效率、心率、血压、左房内径(LAD)、左房舒张末期容积(LAEDV)、左房收缩末期容积(LAESV)、左心房射血分数(LAEF)以及不良反应。结果:两组转复维持有效率比较差异无统计学意义(P0.05);治疗后收缩压、舒张压、LAEDV和LAESV均优于治疗前(P0.05),但治疗后两组组间心率、收缩压、舒张压、LAD、LAEDV、LAESV、LAEF比较差异无统计学意义(P0.05);B组不良反应发生率显著低于A组,两组比较差异具有统计学意义(P0.05)。结论:小剂量胺碘酮联合氯沙坦与大剂量胺碘酮联合氯沙坦治疗阵发性房颤转复效果相当,但是不良反应较少。     

Early gestation dexamethasone alters baroreflex and vascular responses in newborn lambs before hypertension

Exposure of the early gestation ovine fetus to exogenous glucocorticoids induces alterations in postnatal cardiovascular physiology, including hypertension. To determine whether autonomic function and systemic vascular reactivity are altered by in utero programming before the development of systemic hypertension, we examined arterial baroreflex function and in vivo hemodynamic and in vitro vascular responses to vasoactive agents in 10- to 14-day-old newborn lambs exposed to early gestation glucocorticoids. Dexamethasone (Dex, 0.28 mg.kg-1.day-1) or saline was administered to pregnant ewes by intravenous infusion over 48 h beginning at 27 days gestation (term 145 days), and lambs were allowed to deliver (n=6 in each group). Resting mean arterial blood pressure (MABP; 77+/-1 vs. 74+/-3 mmHg) and heart rate (HR; 249+/-9 vs. 226+/-21 beats/min) were similar in Dex-exposed and control animals, respectively. The arterial baroreflex curve, relating changes in HR to MABP, was significantly shifted toward higher pressure in the Dex-exposed lambs although no change in the sensitivity (gain) of the response was seen. In vivo changes in blood pressure in response to bolus doses of ANG II (20, 50, and 100 ng/kg) and phenylephrine (2, 5, and 10 microg/kg) were similar in the two groups. However, Dex lambs displayed greater decreases in MABP in response to ganglionic blockade with tetraethylammonium bromide (10 mg/kg; -30+/-3 vs. -20+/-3 mmHg, P<0.05) and greater increases in MABP after nitric oxide synthase blockade with NG-nitro-L-arginine (25 mg/kg; 23+/-3 vs. 13+/-2 mmHg, P<0.05) compared with control lambs. By in vitro wire myography, mesenteric and femoral artery microvessel contractile responses to KCl were similar, whereas responses to endothelin (in mesenteric) and norepinephrine (in femoral) were significantly attenuated in Dex lambs compared with controls. Femoral vasodilatory responses to forskolin and sodium nitroprusside were similar in the two groups (n=4). These findings suggest that resetting of the baroreflex, accompanied by increased sympathetic activity and altered nitric oxide-mediated compensatory vasodilatory function, may be important contributors to programming of hypertension.     

Attenuation by naloxone of the pressor effects of angiotensin II in conscious cynomolgus monkeys

The effects of naloxone and morphine on mean arterial blood pressure (MBP) and heart rate (HR) responses to angiotensin II (AII) were studied in conscious cynomolgus monkeys. Graded doses of AII (0.3, 1 and 3 micrograms/min for 8-10 min) were infused i.v. 20 min apart, preceded by an i.v. injection of either naloxone (1, 3 or 10 mg/kg), morphine (0.3, 1 or 3 mg/kg) or saline. Pretreatment with naloxone (10 mg/kg) attenuated the pressor response to AII (0.3 or 1 microgram/min) by 25-50% but did not alter similar pressor responses to phenylephrine. Pretreatment with morphine had little or no effect on MBP or HR responses to AII.     

Combined use of dopamine and prostaglandin A1 in patients with acute renal failure and hepatorenal syndrome

Dopamine and prostaglandin A₁ were infused intravenously in 4 patients with the hepatorenal syndrome, in 1 patient with acute tubular necrosis, and 1 patient with cortical necrosis. Large doses of prostaglandin A₁ decreased arterial blood pressure preventing increase in dosage; in contrast, high doses of dopamine elevated blood pressure. When the two drugs were administered conjointly, much larger doses of each agent could be administered without change in arterial blood pressure. Significant improvement of renal function was not observed in any of these critically ill patients during or within 24 hours after dopamine and prostaglandin A₁ administration. This study demonstrated that extremely large doses of these vasodilating agents can be safely administered conjointly.     

Hemodynamic actions of endothelin in conscious and anesthetized dogs

The newly described endogenous peptide, endothelin, was administered to five chronically instrumented conditioned dogs. Endothelin produced significant and simultaneous increases in both heart rate (HR) and mean arterial pressure (MAP) in conscious dogs. Endothelin also produced significant increases in MAP in anesthetized animals. Ganglionic suppression induced by hexamethonium (10 mg/kg) and atropine (0.1 mg/kg) blocked HR responses and markedly inhibited the pressor responses to endothelin in conscious animals. These results suggest that endothelin in part acts to elevate blood pressure and heart rate through modification of autonomic nervous system tone. When endothelin and angiotensin II were administered in mole equivalent doses, angiotensin II produced a pressor response of greater magnitude than did endothelin in conscious animals.     

Initial evaluation of the non-sulfhydryl-containing converting enzyme inhibitor MK-521 in hypertensive humans

MK-521 is a new orally active, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor. Single doses of 2.5, 5.0, 10.0, and 20.0 mg were administered to nine hypertensive patients alternating with placebo. All doses of MK-521 caused profound suppression of ACE activity for more than 24 h and decreased standing diastolic blood pressure for more than 12 h without changes in pulse rate. Although there was no further reduction in blood pressure with doses above 5.0 mg, the duration of action was prolonged for more than 24 h with the higher doses. Serum MK-521 concentrations increased with dosage, and ACE was inhibited maximally at concentrations above 10 ng/ml. In this initial study, MK-521 was well tolerated and proved to be a potent and long-acting antihypertensive agent.     

The potential for interaction of hydrochlorothiazide with garlic in rats

The present study was undertaken to determine the pharmacokinetic and pharmacodynamic interaction of hydrochlorothiazide (HCTZ) with garlic homogenate (GH), in rats. The influence of garlic on pharmacokinetics of HCTZ was studied by HPLC method, while pharmacodynamic interaction was studied using diuretic activity, ECG and BP changes and isoproterenol (ISO) induced myocardial injury. HCTZ was given orally at 10 mg/kg and GH was administered at three different doses of 125, 250 and 500 mg/kg, p.o. The CK-MB, LDH, SOD, catalase and histopathological studies were carried out. The administration of HCTZ in GH pretreated rats found to decrease the QRS duration, RR interval, QT segment, systolic blood pressure, heart rate, serum potassium level, serum LDH and serum CK-MB activities significantly. The diuretic effect of HCTZ was significantly increased in presence of GH; however, kaliuresis was significantly reduced in presence of GH 250 mg/kg. Histopathological studies of heart tissue reveal the protective effect of GH 250 mg/kg in presence or absence of HCTZ during ISO stress to myocardium. The pharmacokinetic studies show that GH increases the bioavailability and half-life, along with decrease in clearance and elimination rate of HCTZ when administered orally. It was concluded that careful addition of garlic in moderate doses might result in beneficial effect during treatment of hypertension in patients with myocardial stress as garlic causes substantial fall in excretion of potassium when compared to HCTZ alone treatment in rats. This could be important in reducing the dose of HCTZ to achieve enhanced therapeutic effect with minimal adverse effect.     

Cardiovascular responses to opioid agonists injected into the nucleus of tractus solitarius of anesthetized cats

It has been proposed that various opiate receptor subtypes mediate different cardiovascular responses to centrally administered opioids. We evaluated this hypothesis in chloralose-urethane anesthetized cats by monitoring the cardiovascular and respiratory responses to relative mu [morphine, morphiceptin, D-Ala2, MePhe4, Gly-ol5 enkephalin (DAGO)] and delta [D-Ala2, D-Leu5enkephalin (DADL)] agonists microinjected (0.5 ul/kg) into the caudal region of the Nucleus of Tractus Solitarius (NTS). Dynorphin (1-13), an endogenous opioid which exhibits selective affinity towards the kappa receptor, was also tested. Dynorphin at a dose of 50 nMol/kg did not alter cardiovascular or respiratory variables. Morphine (10-54 nMol/kg) and DAGO (50 nMol/kg) had no effect on blood pressure, heart rate or respiratory rate; morphiceptin (100-320 nMol/kg) caused tachycardia only at the highest dose. DADL (10-100 nMol/kg) elicited a dose-dependent depression of blood pressure. High doses of DADL depressed heart rate and respiratory rate. The depressor effects of DADL were reversed by low doses of naloxone (0.1 mg/kg). This dose of naloxone also elicited pressor responses in cats treated with the other opioids and reversed the morphiceptin-induced tachycardia. These data indicate that opioid agonists differ with regard to their cardiovascular and respiratory effects following microinjection into the NTS of anesthetized cats, with the delta agonist DADL showing greatest activity.     

The effects of acebutolol alone and in combination with furosemide or hydralazine in experimentally induced hypertensive G-minipigs

Experimentally induced hypertensive G-minipigs were used for assessing the antihypertensive effects of acebutolol, a cardioselective beta-adrenergic blocking agent. In the acute experiment, six females were used. Acebutolol (3 mg/kg, i.v.) alone or in combination with furosemide (1 mg/kg, i.v.) or hydralazine (1 mg/kg, i.v.) was administered through an implanted catheter. In the chronic experiments, five females received oral acebutolol (100-200 mg/day). The blood pressure, heart rate, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were used as parameters. In the acute experiment, there were no marked changes in the blood pressure or heart rate during the nondosing period. Acebutolol alone caused a marked decrease in the blood pressure and heart rate. In the two combination tests, combined administration with acebutolol and furosemide had a greater effect on the blood pressure and heart rate than did acebutolol alone. A combined acebutolol and hydralazine regimen caused a slight reduction not only in the blood pressure, but also in the heart rate compared with acebutolol alone. PRA and PAC remained essentially constant, with minor fluctuations, throughout the nondosing period. Following the injection of acebutolol alone, PRA showed an elevation with a significant rise after three hours and PAC showed a tendency to increase. PRA and PAC generally tended to increase in the case of combined administration with furosemide or hydralazine, but these tendencies were less conspicuous than with acebutolol alone. On the other hand, chronic treatment with acebutolol produced a significant decrease in the heart rate from two weeks after the administration and in the blood pressure from four weeks.(ABSTRACT TRUNCATED AT 250 WORDS)