β2-Adrenoceptors in Rat Liver Microcirculation

1. Rat liver sinusoids were observed by a microscopic in vivo transillumination method. The diameter of liver sinusoids and intrasinusoid erythrocyte flow velocities were measured quantitatively by a close-circuit television technique. 2. Both isoprenaline and the selective β₂-adrenoceptor agonist terbutaline produced a concentration-dependent dilatation of liver sinusoids and slowed erythrocyte flow velocity. The effects of isoprenaline and terbutaline were antagonized by propranolol but not by the selective β₁-adrenoceptor antagonist atenolol. Propranolol alone produced constriction of the liver sinusoids and increased erythrocyte flow velocity; these effects were not produced by atenolol. 3. The percentage dilatations produced by isoprenaline alone, isoprenaline in the presence of phenoxybenzamine and isoprenaline in the presence of phenylephrine-induced constriction were similar. 4. It is proposed that the β-adrenoceptors in liver sinusoids are of the β₂-type, and their physiological role was to counteract constrictor responses produced by a-adrenoceptor activity.     

Comparison of the cardiovascular effects of meptazinol and naloxone following haemorrhagic shock in rats and cats.

The cardiovascular effects of the opioid mixed agonist-antagonist, meptazinol, and the opioid antagonist, naloxone, have been evaluated in conscious rats, anaesthetized rats and anaesthetized cats following the induction of haemorrhagic shock. The mean arterial pressure of conscious rats decreased by 17-29 mmHg following a haemorrhage of 20% of blood volume. Meptazinol (17 mg kg-1, i.m.) administered after haemorrhage evoked a rapid and sustained increase in mean arterial pressure to pre-haemorrhage levels. Naloxone (10 mg kg-1, i.v.) also increased mean arterial pressure to a level significantly higher than post-haemorrhage values. Neither haemorrhage nor subsequent drug treatments evoked significant changes in the heart rates of conscious rats. In anaesthetized rats, 20% haemorrhage evoked decreases in mean arterial pressure, heart rate and cardiac output. Blood flow to the heart, skin, skeletal muscle, kidneys, spleen and liver (arterial) was decreased. Meptazinol and naloxone increased blood pressure and total peripheral resistance, but did not significantly alter heart rate or cardiac output. Hepatic arterial flow decreased further in both drug and vehicle treated groups. In addition meptazinol slightly reduced skeletal muscle flow. In anaesthetized cats 40% haemorrhage decreased mean arterial pressure by 46 +/- 3 mmHg. An intravenous infusion of either meptazinol or naloxone (cumulative 2 mg kg-1, i.v.) partially restored blood pressure. In experimental animal models of haemorrhagic shock, meptazinol has a similar cardiovascular profile to naloxone. The established analgesic activity of meptazinol may confer an advantage in some shock states.     

Effects of salvianolic scid A on plantar microcirculation and peripheral nerve function in diabetic rats

It has been found that dinitrosyl iron complexes with glutathione (DNIC-GS) injected into the blood flow of rats at a dose of 0.05 μmoles/kg prior to hemorrhage significantly improve cardiac function under conditions of hemorrhagic shock manifested in increased stroke volume, left ventricular work and cardiac output to a level exceeding control values 1.5-fold. Enhanced myocardial contractile activity leads to a situation where mean arterial pressure does not decrease further despite the significant decrease of total peripheral resistance. The decrease of total peripheral vascular resistance of the vascular system under vasodilating effects of DNIC-GS used as nitric oxide donors improves microcirculation in experimental rats judging from increased rates of blood flow and low degree of erythrocyte aggregation. Pretreatment of rats with the complexes significantly increases survival (by 21%) under conditions of hemorrhagic shock. It is suggested that beneficial effects of DNIC-GS on systemic circulation parameters under conditions of hemorrhagic shock are determined by their antioxidant activity and the ability to induce S-nitrosylation of proteins.     

主动脉内球囊反搏治疗心肌梗死合并心源性休克的价值探讨

目的：探讨主动脉内球囊反搏治疗心肌梗死合并心源性休克的临床价值。方法选取本院收治的80例心肌梗死合并心源性休克患者作为研究对象,随机分为两组,各40例,观察组采用主动脉内球囊反搏,对照组采用急诊心脏介入溶栓治疗,比较两组治疗后的心排血量、平均动脉压变化情况及治疗后出血相关并发症。结果观察组心排血量、平均动脉压显著高于对照组,差异有统计学意义（P＜0.05）,观察组消化道出血、皮下血肿及泌尿道出血的发生率显著低于对照组,差异有统计学意义（P＜0.05）。结论主动脉内球囊扩张能有效提高心肌梗死合并心源性休克患者的心排血量及动脉血压,减少出血相关并发症,值得临床重视。     

POTASSIUM CHANNEL ACTIVATION IMPROVES BLOOD FLOW PATTERN OF CONSCIOUS RATS IN CUTANEOUS MICROCIRCULATION

1. A dose-dependent mean arterial blood pressure reduction (tailcuff method) to an intravenously administered potassium channel activator (22 or 24 micrograms/kg bw) was found in conscious rats. 2. Intravital microscopic analysis of skin microcirculation in conscious rats was performed with respect to erythrocyte flow velocity and diameters of capillaries. There was a dose-dependent increase of erythrocyte flow velocity; diameters of capillaries were dilated following a dosage of 6 and 12 micrograms/kg bw, but constricted following a dosage of 24 micrograms/kg bw. 3. Frequency distributions of velocity ranges in capillaries under observation (real time video recordings) proved that the increase of microvascular perfusion is manifested by a shift of maximal values to increasing velocity ranges. 4. It is concluded that potassium channel activation plays an important role in the local regulation of perfusion on the peripheral circulation.     

大量抗坏血酸注射液对心血管系统的作用

本文报导大量抗坏血酸注射液(injectio acidi ascorbici,以下簡称IAA)对动物血压、心脏及血管的影响。IAA为用碳酸氫鈉中和的10%抗坏血酸灭菌溶液,pH約为5.6,內加焦亚硫酸鈉作稳定剂。靜脉注射IAA 0.2克/公斤及0.4克/公斤可使麻醉犬、猫和家冤动脉血压輕度短时上升;在因手术創伤、失血及数种降压莉物(氯丙嗪、亚硝酸鈉、組織胺、罌粟碱)所致低血压的动物,IAA的升压作用較为明显持久。同剂量抗坏血酸溶液(solution acidiascorbici,以下簡称SAA)靜脉注射常引起血压下降,用碳酸氫鈉将SAA中和后即有升压作用,焦亚硫酸鈉无升压作用,故IAA的升压作用是中和后的抗坏血酸所引起。靜脉注射IAA0.2克/公斤可增加麻醉犬心搏量、心輸出量及心脏指数,对总外周阻力无明显影响;对在体冤心亦呈現兴奋作用。1:1,000和1:500的IAA灌流离体冤心后,可見心縮振幅加大,心率略增,冠脉流量增多。IAA对离体冤耳、腎、下肢血管无明显影响。在体冤下肢及腎血管血流量在血压上升时均有增加。犬脾容积在IAA注射后有輕度扩张現象,而SAA却使脾容积短时減少。实驗結果表明,IAA的升压作用主要是由于心脏功能改善,心輸出量增加所致。     

Effect of Shenfu injection on microcirculation effect index in early-and middle-stage of cardiogenic shock rats

OBJECTIVE Shenfu injection(SFI)is an effective treatment of cardiogenic shock,the pathology of the central link was microcirculation disturbance.However,whether the microcirculation status of the early-and mid-stage of cardiogenic shock has any difference is unclear.This study aimed to observe the effect of SFI on the microcirculatory disturbance in mesentery for early-and mid-stage of cardiogenic shock rat.METHODS The early-and mid-stage model of cardiogenic shock was established by ligating the ending or root of left anterior descending coronary arteries(LADCA).The rats were randomly divided into 9 groups,ie control group,early-stage model group,mid-stage model group,3 early medicated groups and 3 mid medicated groups(the dosage was 1,3.33,10 mL·kg~(-1) SFI for cardiogenic shock rats of early-and mid-stage,respectively).Parameters in mesenteric microcirculation,such as velocity of RBCs in venules,diameters of venules,the count of leukocyte adhesion and vascular permeability which calculated by FITC-dextran leakage were observed through an GeneandiM2 inverted intravital microscope and high-speed video camera system.RESULTS The cardiogenic shock induced by ligating the LADCA resulted in a number of responses in microcirculation,including a significant increase in the counts of adhesive leukocytes,narrowing of the vascular diameter,decrease in the velocity of RBCs and dextran efflux.All of the above parameters for early-stage cardiogenic shock rats were attenuated by the treatment with SFI,especially the dosage of 10 mL·kg~(-1).While SFI had no apparent time-effect on the vascular diameter and vascular permeability in mesentery for mid-stage cardiogenic shock rats.CONCLUSION The microcirculation status of the early-and mid-stage of cardiogenic shock rats were quite different.The efficacy of early treatment with SFI was more obvious than the mid administration,which could provide experimental and theoretical basis for the patients with cardiogenic shock in an earlier time.     

Haemodynamic effects of salbutamol in patients with acute myocardial infarction and severe left ventricular dysfunction

The haemodynamic effects of salbutamol infusions at rates of 10,20, and 40 micrograms/min were measured in 11 patients with acute myocardial infarction complicated by left ventricular failure. Four patients also had cardiogenic shock. Consistent increases were observed in cardiac outputs at all doses (up to 56% at 40 micrograms/min), while the mean systemic arterial pressure fell slightly (average 5 mm Hg), implying a reduction in peripheral vascular resistance. Changes in right atrial pressure and indirect left atrial pressure (measured as pulmonary artery end-diastolic pressure) were small and not significant. Analysis of data from individual patients showed that the greatest increment in cardiac output was reached at 10 micrograms/min in two cases, 20 microgram/min in three, and 40 micrograms/min in the remaining six. Heart rate at these doses increased by an average of only 10 beats/min. Salbutamol failed to reduce left ventricular filling pressure and cannot be recommended for the treatment of pulmonary oedema in acute myocardial infarction. The increase in cardiac output, however, was considerable, so that the drug may be important in the management of low-output states. This action is probably a result of peripheral arteriolar dilatation (itself a result of beta 2-adrenoreceptor stimulation) and is achieved with little alteration in the principal determinants of myocardial oxygen requirement.     

The protective action of allopurinol in an experimental model of haemorrhagic shock and reperfusion.

Haemorrhagic shock was induced in anaesthetized, open-chest dogs by controlled arterial bleeding, sufficient to reduce and maintain mean arterial blood pressure at 40 mmHg for 30 min. The blood volume was then restored to the pre-shock level by rapid, intravenous reinfusion of the blood shed during the shock period. Haemorrhagic shock produced significant haemodynamic changes, characterized by a marked depression of myocardial function. Cardiac output (1226 +/- 57 ml min-1), peak aortic blood flow (6030 +/- 383 ml min-1) and maximum rate of rise of left ventricular pressure (2708 +/- 264 mmHg s-1) were all reduced by more than 50%. The haemodynamic profile was markedly improved by reinfusion of shed blood but this improvement was not sustained. There was a gradual decline such that 50% of the untreated animals suffered complete circulatory collapse and death between 60 and 120 min following reinfusion. Neither haemorrhagic shock, nor reinfusion of shed blood produced any consistent or significant changes in the myocardial adenine nucleotide pool. The ATP, ADP and AMP levels were, respectively, 25.9 +/- 4.2; 15.6 +/- 1.0; 4.3 +/- 1.9 nmol g-1 protein, before haemorrhagic shock; 21.6 +/- 3.4; 21.5 +/- 2.5; 10.2 +/- 2.7 nmol g-1 protein, after 30 min haemorrhagic shock; and 29.9 +/- 3.9; 16.5 +/- 1.2; 4.2 +/- 1.1 nmol g-1 protein, 60 min following reinfusion of shed blood. Pretreatment with allopurinol (50.0 mg kg-1 i.v.), 60 min before inducing haemorrhagic shock, had no significant effect upon the haemodynamic response to shock, but did prevent the gradual decline seen following reinfusion in the untreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

主动脉内球囊反搏术治疗急性心肌梗死并心源性休克21例体会

目的探讨主动脉球囊反搏(intra-aortic balloon pump,IABP)治疗急性心肌梗死并心源性休克的临床疗效。方法 2008年2月至2011年3月间我院使用IABP治疗21例急性心肌梗死并心源性休克患者。观察应用IABP前后平均动脉压(MAP)、尿量、心率、多巴胺及多巴酚丁胺剂量变化。结果应用IABP治疗后患者的平均动脉压(MAP)升高、尿量增多、心率减慢、多巴胺及多巴酚丁胺剂量减少,治疗前后两组各指标变化幅度明显差异有统计学意义。结论急性心肌梗死并心源性休克患者予以IABP治疗,能增加冠状动脉灌注,改善心肌血供,降低左心室后负荷,从而改善心功能,治疗心源性休克。     

β2-Mediated Changes in Central Haemodynamics,Coronary Circulation and Myocardial Metabolism in Canine

Abstract: The combined effect of terbutaline on systemic and coronary circulation was investigated in dogs to clarify its influence on myocardial oxygen supply and lactate balance. The dogs were anaesthetized and the chest opened. Coronary sinus blood flow and cardiac output were monitored by thermodilution, aortic pressure was measured by tip-transducer and heart rate by RR-interval on ECG, coronary sinus blood were analyzed for lactate, oxygen and carbon dioxide. Terbutaline caused a substantial systemic vasodilation and an increased heart rate, the total external cardiac work increased to a minor degree. Terbutaline increased arterial lactate concentration. Coronary vascular resistance was reduced after terbutaline. Even if myocardial perfusion pressure was reduced and an increased external cardiac work was present, no signs of myocardial distress was observed in lactate metabolism or coronary sinus oxygen content. In fact a tendency to increased myocardial aerobic metabolism was observed, as myocardial lactate consumption increased after terbutaline. Terbutaline seems to be a coronary vasodilator in dogs. However, the demand for oxygen secondary to both an increase in cardiac work and aerobic metabolism can be harzardous to the potentially ischaemic myocardium.     

Beta 2-mediated changes in central haemodynamics, coronary circulation and myocardial metabolism in canine

The combined effect of terbutaline on systemic and coronary circulation was investigated in dogs to clarify its influence on myocardial oxygen supply and lactate balance. The dogs were anaesthetized and the chest opened. Coronary sinus blood flow and cardiac output were monitored by thermodilution, aortic pressure was measured by tip-transducer and heart rate by RR-interval on ECG, coronary sinus blood were analyzed for lactate, oxygen and carbon dioxide. Terbutaline caused a substantial systemic vasodilation and an increased heart rate, the total external cardiac work increased to a minor degree. Terbutaline increased arterial lactate concentration. Coronary vascular resistance was reduced after terbutaline. Even if myocardial perfusion pressure was reduced and an increased external cardiac work was present, no signs of myocardial distress was observed in lactate metabolism or coronary sinus oxygen content. In fact a tendency to increased myocardial aerobic metabolism was observed, as myocardial lactate consumption increased after terbutaline. Terbutaline seems to be a coronary vasodilator in dogs. However, the demand for oxygen secondary to both an increase in cardiac work and aerobic metabolism can be hazardous to the potentially ischaemic myocardium.     

Effect of prostaglandins F2alpha and E1 on systemic and regional hemodynamics]

In experiments with anesthetized female-rats the influence of intravenous prostaglandins F2alpha (40 mg/kg) and Ei (10 mg/kg) on the cardiac output (by the method of dye dilution) and on the blood flow distribution among organs and tissues (by the method of Rb86 distribution) was studied. Prostaglandin F2alpha increased the arterial pressure, cardiac output along with the volume of the circulating plasma and reduced the total peripheral resistance. The hypertensive effect of prostaglandin F 2alpha is, under the circumstances, conditioned by the increased cardiac output and this substance is also instrumental in augmenting the proportion of the blood flow going to the digestive tract, skeletal muscles and, at the same time, in reducing its share flowing to the liver, spleen, skin and the uterus. Prostaglandin E1 reduced the blood pressure and total peripheral resistance and raised the cardiac output. The hypotensive effec of prostaglandin Ei is due to the fall of the total peripheral resistance. This compound tends to increase the part of the cardiac output that goes to supply the intesine, liver, lungs, myocardium and skeletal muscles and cuts down that part which caters for the stomach and kidneys.     

Comparison of the ability of nicardipine, theophylline and zaprinast to restore cardiovascular haemodynamics following inhibition of nitric oxide synthesis.

1. The use of pharmacological inhibitors of nitric oxide (NO) synthesis to treat patients with septic shock is limited by the observation that they cause a fall in cardiac output in some subjects. The aim of this work was to investigate this fall and to test whether it was reversible by subsequent administration of nicardipine, theophylline or the cyclic GMP-selective phosphodiesterase inhibitor, zaprinast (M&B 22948). 2. In pentobarbitone-anaesthetized pigs, haemodynamic indices were measured before and after intravenous administration of NG-nitro-L-arginine methyl ester (L-NAME) in a dose-response protocol (0.2-20 mg kg-1; n = 6) and as a single bolus of 10 mg kg-1 either alone or followed by increasing doses of nicardipine, theophylline or zaprinast (n = 8 in each group). 3. L-NAME caused a dose-dependent rise in systemic vascular resistance and mean systemic arterial pressure and a dose-dependent fall in cardiac output. A single bolus of L-NAME (10 mg kg-1) produced these effects within 15 min. 4. Subsequent administration of nicardipine (0.05-0.2 mg kg-1) caused complete reversal of systemic vasoconstriction and hypertension and in doing so completely restored cardiac output. Theophylline (7.5-10 mg kg-1) partially reversed the rise in systemic vascular resistance and partially restored cardiac output but the effect was small compared to that of nicardipine. Zaprinast (1-5 mg kg-1) had no significant effect on any of these variables.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of vasodilators on microcirculation of the rat cremaster muscle: a microscopic method for screening drugs.

Effects of vasodilating drugs on microcirculation of the rat cremaster muscle were investigated microscopically. Topical application and intravenous injection of papaverine produced dilatation of arterioles. Cyclandelate applied topically dilated the arterioles to a considerable extent. Topical application of bamethan induced arteriolar dilatation while bamethan given intravenously constricted the arterioles. Kallikrein applied topically induced a slight dilatation of arterioles, and intravenous administration of kallikrein produced an appreciable vasodilatation. Topical administration of bradykinin produced a vasodilatation of arterioles of the rat cremaster muscle. These results indicate that direct action of a drug on the microcirculation can be properly evaluated by the microscopic method in the rat cremater muscle, if the drug is applied topically, in the vicinity of small vessels under study.     

Effects of alpha1-acid glycoprotein in combination with catecholamines on hemorrhagic hypovolemic shock in rats

To determine whether the beneficial effects of catecholamines on the variables of hemorrhagic hypovolemic shock are augmented by coadministration of alpha1-acid glycoprotein during resuscitation, alpha1-acid glycoprotein (200 mg/kg), a placebo formulation or Ringer's solution was infused in a rat model of hemorrhagic hypovolemic shock for 1 h concomitantly with either norepinephrine (CAS 51-40-1; 0.1, 0.3, 1 microg x kg(-1) x min(-1)) or dopamine (CAS 62-31-7; 5, 10, 15 microg x kg(-1) x min(-1)). Resuscitation with norepinephrine or dopamine alone was continued for a further 4 h. Mean arterial blood pressure, cardiac output, stroke volume, heart rate and total peripheral vascular resistance were measured during the entire 5-h period. The combination of dopamine or norepinephrine with alpha1-acid glycoprotein more effectively restored mean arterial blood pressure and cardiac output than analogous combinations with placebo formulation or Ringer's solution. So co-administration with alpha1-acid glycoprotein considerably augments the beneficial effects of catecholamines on the main variables of hemorrhagic hypovolemic shock.     

Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors

BACKGROUND AND PURPOSE: Hyperdynamic circulation and mesenteric hyperaemia are found in cirrhosis. To delineate the role of endocannabinoids in these changes, we examined the cardiovascular effects of anandamide, AM251 (CB(1) antagonist), AM630 (CB(2) antagonist) and capsazepine (VR1 antagonist), in a rat model of cirrhosis. EXPERIMENTAL APPROACH: Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, diameters of mesenteric arteriole and venule (intravital microscopy), arterial pressure, cardiac output, systemic vascular resistance and superior mesenteric artery (SMA) flow were measured after anandamide, AM251 (with or without anandamide), AM630 and capsazepine administration. CB(1), CB(2) and VR1 receptor expression in SMA was assessed by western blot and RT-PCR. KEY RESULTS: Anandamide increased mesenteric vessel diameter and flow, and cardiac output in cirrhotic rats, but did not affect controls. Anandamide induced a triphasic arterial pressure response in controls, but this pattern differed markedly in cirrhotic rats. Pre-administration of AM251 blocked the effects of anandamide. AM251 (without anandamide) increased arterial pressure and systemic vascular resistance, constricted mesenteric arterioles, decreased SMA flow and changed cardiac output in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac output and mesenteric arteriolar diameter and flow, and increased systemic vascular resistance in cirrhotic rats, but lacked effect in controls. Expression of CB(1) and VR1 receptor proteins were increased in cirrhotic rats. AM630 did not affect any cardiovascular parameter in either group. CONCLUSIONS AND IMPLICATIONS: These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB(1)- and VR1-mediated mechanisms.     

The effect of diuretic drugs on lymph flow in experimental ascites

The effect of several diuretic agents on thoracic duct and right lymph trunk lymph flow, and on some other parameters was examined in normal dogs and dogs with ascites produced by the constriction of inferior cava vein. In normal animals furosemide and etacrynic acid in diuretic doses did not influence thoracic duct lymph flow and reduced slightly arterial pressure and GFR (creatinine clearance). Hydrochlorothiazide increased slightly thoracic duct flow. Neither of the drugs had any significant influence on right trunk lymph flow. In dogs with ascites all drugs tested (furosemide, etacrynic acid and mercurophylline) reduced lymph flow in the thoracic duct but had no effect on the flow in the right trunk. The drugs reduced markedly arterial and inferior cava venous pressure. It is concluded that their effect on ascites is not based on enhanced lymphatic absorption and transport but mainly on the reduction of fluid and protein leakage from the liver sinusoids.     

THE HAEMODYNAMIC EFFECTS OF QUAZODINE, A CARDIAC STIMULANT, IN EXPERIMENTAL E. COLI ENDOTOXIN SHOCK IN THE CAT

SUMMARY 1. Intravenous injections of quazodine (6,7-dimethoxy-4-ethylquinazoline, 0–5 mg/kg per min) in pentobarbitone-anaesthetized cats increased heart rate, the maximum rate of pressure development in the left ventricle (LV dP/dt max.), cardiac output and myocardial blood flow, and decreased systemic arterial blood pressure. The effects of this cardiac stimulant were examined 1, 2, and 3 h after the intravenous administration of 2 mg/kg of E. coli endotoxin.
2. During the endotoxin shock phase (> 1 h after endotoxin) the most pronounced effects were decreases in systemic blood pressure and cardiac output and a severe metabolic acidosis.
3. Quazodine failed to increase cardiac output during endotoxin shock and the effects on the heart rate and LV dp/dt max. were much reduced. In contrast, quazodine-induced vasodilatation was much more marked.
4. It is concluded that there is profound myocardial depression in severe endotoxin shock in the cat and that this cannot be significantly modified by quazodine.     

The effects of nisoldipine (Bay K 5552) on cardiovascular performance and regional blood flow in pentobarbital-anaesthetized pigs with or without beta-adrenoceptor blockade.

The effects of the 1,4-dihydropyridine derivative nisoldipine, infused intravenously (i.v.) at 3 different rates (0.25, 0.5 and 1.0 microgram kg-1 min-1), were studied in anaesthetized pigs on cardiovascular performance with or without beta-adrenoceptor blockade produced by propranolol. Nisoldipine caused dose-dependent decreases in arterial blood pressure (30%), systemic vascular resistance (30%) and left ventricular filling pressure (15%), but raised heart rate (25%) and LV dP/dt max (20%). Cardiac output was not significantly affected. Transmural myocardial blood flow and vascular conductances increased dose-dependently after nisoldipine. The elevation in blood flow to the left ventricle favoured epicardial layers. Endocardial blood flow showed small increases as the changes in conductance of the endocardial layer more than compensated for the loss in perfusion pressure. The endo-epi blood flow ratio decreased from 1.16 +/- 0.05 to 0.70 +/- 0.01. Myocardial O2-consumption was unaltered as the decrease in arterial-coronary venous O2-content difference (30%) was balanced by the increase in transmural blood flow. Nisoldipine increased blood flow to skeletal muscle (500%), stomach (50%) and adrenals (25%), but decreased that to the liver (50%), spleen (25%) and kidneys (25%). No changes were noticed in the small intestine, skin and brain. In spite of differential effects on blood flow, vascular conductance in all organs and tissues, with the exception of the liver, increased. After beta-adrenoceptor blockade the responses of mean arterial blood pressure, cardiac output and systemic vascular resistance to nisoldipine remained virtually unchanged, but the elevations in heart rate and LV dP/dt max were abolished, as was the decrease in left ventricular filling pressure. A higher dose of nisoldipine was required after beta-adrenoceptor blockade to elicit significant vasodilatation in the epi- and endocardial layers. However, the reduction in endo-epi blood flow ratio by nisoldipine was not affected by propranolol. Myocardial O2-consumption tended to decrease as the diminution in the arterial-coronary venous O2-content difference (30%) slightly exceeded the increase of left ventricular blood flow (30%). Except for the brain and liver, effects of nisoldipine on regional vascular conductances were attenuated after beta-adrenoceptor blockade.