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Biomedical subjects

O E Brodde

Publications and source records attributed to O E Brodde.

At least 55 records · Page 3Linked to original sources
PubMed1997

Chronic terbutaline treatment desensitizes beta-adrenergic inhibition of lymphocyte activation in healthy volunteers.

1. A substantial body of evidence has accumulated that beta-adrenoceptor mediated increases in human lymphocyte cyclic AMP can inhibit activation of resting lymphocytes. The aim of this study was to determine whether this effect might desensitize during chronic beta-adrenoceptor agonist treatment. We assessed the effects of 2 weeks treatment with the beta 2-adrenoceptor agonist terbutaline (3 x 5 mg day-1 p.o.) on isoprenaline-induced inhibition of concanavalin A-evoked lymphocyte activation in nine healthy male volunteers. Lymphocyte activation was determined by [3H]-thymidine incorporation (as a measure of proliferation), and inositol phosphate formation was assessed in [3H]-myo-inositol prelabelled lymphocytes in the presence of 10 mM LiCl. 2. Terbutaline treatment caused a significant reduction in isoprenaline (1 nM-10 microM)-induced increases in lymphocyte cyclic AMP content; the maximal increase was 14 +/- 3 pmol/10(6) cells before and 7 +/- 2 pmol/10(6) cells (n = 9, P < 0.05) after terbutaline treatment. 3. The mitogen concanavalin A (Con A, 1-32 micrograms ml-1)-induced increase in inositol phosphate formation was significantly enhanced after terbutaline treatment (max. increase before treatment: 255 +/- 25% above basal; after treatment 453 +/- 16% above basal; n = 9, P < 0.001), while isoprenaline (1 nM-10 microM)-induced inhibition of Con A (16 micrograms ml-1)-evoked increases in inositol phosphate formation was significantly reduced after the terbutaline treatment (max. inhibition before treatment: 22 +/- 4%; after treatment 9 +/- 1%, n = 9, P < 0.01). 4. Con A (1.25-10 micrograms ml-1)-induced increases in [3H]-thymidine incorporation into the lymphocytes (as a measure of proliferation) was not affected by the terbutaline treatment. On the other hand, isoprenaline (1 nM-1 microM)-induced inhibition of Con A (5 micrograms ml-1)-evoked lymphocyte proliferation (max. inhibition: 33 +/- 7%, n = 9) was almost completely abolished after the terbutaline treatment. 5. We conclude that chronic treatment with terbutaline desensitizes lymphocyte beta 2-adrenoceptors and, therefore, the inhibitory effect of cyclic AMP on lymphocyte activation.

Adrenergic beta-Agonists↗
PubMed1997

Functional role of beta2-adrenoceptors in the transplanted human heart.

In the transplanted human heart, beta-adrenoceptor subtypes change with time after transplantation: beta1-adrenoceptors tend to decline, whereas beta2-adrenoceptors are upregulated. The aim of this study was to determine whether, in the transplanted human heart, stimulation of beta2-adrenoceptors can induce heart-rate increases. For this purpose, we assessed in eight heart-transplant recipients (mean posttransplant time: 932 days) the effects of infusion of graded doses of isoprenaline (3.5-35 ng/kg/min) 120 min after pretreatment with the beta1-adrenoceptor antagonist bisoprolol (10 mg p.o.; beta1-adrenoceptor occupancy approximately 80%; beta2-adrenoceptor occupancy <5%) on heart rate in the recipient's native (innervated) and transplanted (denervated) sinus nodes. Isoprenaline, acting under these conditions predominantly at beta2-adrenoceptors, increased heart rate both in the recipient's transplanted and native sinus nodes in a dose-dependent manner; at each dose, increases were significantly higher in the transplanted than in the native sinus node. ED20 values (dose to increase heart rate by 20 beats/min) in the transplanted sinus node were 22.2 +/- 1.8 ng/kg/min, and in the native, >35 ng/kg/min (p < 0.01). We conclude that in the transplanted human heart, beta2-adrenoceptor stimulation does evoke increases in heart rate. The enhanced response to isoprenaline in the transplanted sinus node could be caused by the upregulated beta2-adrenoceptors or by the fact that during isoprenaline infusion, vagal activity increases, thus blunting the response in the native (innervated) but not in the transplanted (denervated) sinus node.

Adrenergic beta-Agonists↗
PubMed1997

Tocolytic therapy with fenoterol induces selective down-regulation of beta-adrenergic receptors in human myometrium.

Tocolytic therapy with beta-adrenergic receptor agonists is a standard regimen to prevent preterm birth. Agonists exposure of beta-adrenergic receptors causes receptor desensitization in other organs, and this may limit the therapeutic value of beta-adrenergic receptor agonists. To study the effects of prolonged beta-adrenergic agonist treatment in human myometrium, we obtained biopsies during Caesarean section of 14 pregnant patients who had received fenoterol for at least 5 days and 14 untreated pregnant controls. The densities of total beta-adrenergic receptors, which are mainly of the beta 2-subtype as assessed by [125I]iodo-cyanopindolol binding in crude membrane fractions, were more than 50% smaller in women receiving fenoterol, whereas alpha 2-adrenergic receptor densities were similar. Gs and Gi G-protein alpha-subunit densities were unaltered as assessed by Western blotting and pertussis toxin-catalyzed [32P]ADP-ribosylation. beta-Adrenergic receptor kinase (beta ARK) activity, as determined using bovine rhodopsin as the substrate, was the same in the two groups. Adenylyl cyclase activities in the presence of guanine nucleotides, NaF, forskolin, or Mn+2 were also not altered by fenoterol treatment. The messenger RNA (mRNA) concentrations of beta 2-adrenergic receptors, beta ARK-I and glyceraldehyde-3-phosphate dehydrogenase (as a reference), as determined by quantitative PCR, were unaffected by fenoterol treatment. We conclude that tocolysis with fenoterol results in a selective down-regulation of myometrial beta-adrenergic receptors, which is not associated with a reduction in the respective mRNA concentrations or alterations of alpha 2-adrenergic receptors, Gs and Gi alpha-subunits, or beta ARK activity or mRNA.

Adult↗
PubMed1997

Imaging beta-adrenoceptors in the human brain with (S)-1'-[18F]fluorocarazolol.

UNLABELLED: We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral beta-adrenoceptors because (S)-1'-[18F]fluorocarazolol has a higher affinity to beta-adrenoceptors than to serotonergic receptors (pKi beta 1 9.4, beta 2 10.0, 5HT1A 7.4, 5HT1B 8.1) and rapidly crosses the blood-brain barrier. METHODS: The (S)-[18F]fluorocarazolol (74 MBq, > 37 TBq/mmol) was intravenously administered to healthy volunteers on two separate occasions with an interval of at least 1 wk. The initial injection was without pretreatment, but before the second injection, the volunteers received the beta blocker (+/-)-pindolol (3 x 5 mg orally, during 18 hr). The brain was studied with a PET camera in dynamic mode. RESULTS: Uptake of radioactivity delineated gray matter and was particularly high in the posterior cingulate, precuneus and striatum. Low uptake occurred in the thalamus, whereas the lowest uptake was observed in the white matter of the corpus callosum. After pindolol pretreatment, uptake was reduced and its distribution became homogeneous throughout the brain. The ratio of total-to-nonspecific binding was about 2 at 60 min, increasing to 2.5-2.75 at longer intervals. CONCLUSION: Fluorocarazolol is the first radioligand that can visualize cerebral beta-adrenoceptors and may enable monitoring of these binding sites during disease.

Adrenergic beta-Antagonists↗
PubMed1996

Chronic treatment with carbachol sensitizes the myocardium to cAMP-induced arrhythmia.

BACKGROUND: The present study investigated biochemical and functional consequences of chronic activation of the inhibitory Gi alpha-coupled adenylyl cyclase pathway in the heart. METHODS AND RESULTS: Rats (220 to 260 g) were treated with 4-day infusions of the M-cholinoceptor agonist carbachol (9.6 mg/kg per day) or vehicle. An additional group that received the beta-adrenoceptor agonist isoprenaline (2.4 mg/kg per day) served as control. The main finding was that chronic infusion of carbachol led to a marked increase in isoprenaline- or forskolin-induced arrhythmia in electrically driven papillary muscles (in vitro). Compared with control, the potency of isoprenaline and forskolin to induce arrhythmia in cardiac preparations from carbachol-treated rats was increased 36- and 2.2-fold and the efficacy was increased 7.3- and 2.3-fold, respectively. The potency of carbachol to antagonize the isoprenaline- and forskolin-induced arrhythmia was decreased 30-fold. These changes were accompanied by a decrease in left ventricular M-cholinoceptor density by 15% (P < .05) and a decrease in pertussis toxin-sensitive G proteins (Gi alpha) by 26% (P < .05) without a decrease in the corresponding mRNAs. beta-Adrenoceptor density and basal and stimulated adenylyl cyclase activity remained unchanged. In contrast, isoprenaline infusion induced a decrease in arrhythmogenic potency of forskolin (P = NS), which was accompanied by a decrease in beta-adrenoceptor density, an increase in Gi alpha protein and mRNA levels, and a decrease in basal and stimulated adenylyl cyclase activity. CONCLUSIONS: Chronic parasympathetic activation sensitizes the myocardium to cAMP-induced arrhythmia. These changes may be due to quantitative alterations in functional Gi alpha.

Adenylate Cyclase Toxin↗
PubMed1996

Endothelin-induced inositol phosphate formation in rat kidney. Studies on receptor subtypes, G-proteins and regulation during ontogenesis.

The aim of this study was to characterize the properties of endothelin (ET)-receptor subtypes mediating inositol phosphate (IP)-formation in rat kidney and their regulation during ontogenesis. In renal cortical slices of adult rats (12-16 weeks old) ET's concentration-dependently increased IP-formation with an order of potency ET-1 >> ET-3. While the non-selective ET-receptor antagonist bosentan (10 microM) completely suppressed ET-induced IP-formation, the ETA-receptor antagonist BQ-123 (10 microM) inhibited it only by 70%, the ETB-receptor antagonist IRL 1038 (1 microM) by 25%; combined application of BQ-123 + IRL 1038 caused complete inhibition of ET-1-induced IP-formation. Pretreatment of isolated renal cells with pertussis toxin (PTX, 500 ng/ml) overnight did not attenuate but significantly increased ET-1-induced IP-formation. Ontogenetic studies in renal sites from neonatal, 1, 2, 3, 6, 12 and 24 weeks old rats revealed that ET-1-induced IP-formation maturation-dependently declined being highest in neonatal rats (increase: 169% over basal) and lowest in 24 weeks old rats (increase: 47% over basal). This decline in ET-induced IP-formation was accompanied by a decrease in renal ET-receptor number and the amount of immunodetectable Gq/11 (assessed by Western-blotting using the QL-antiserum). Moreover, ET-receptor subtypes changed during the maturation process: from neonates to 12 weeks old rats number and functional responsiveness of ETA-receptors declined, while that of ETB-receptors increased. We conclude that in adult rat renal cortex ET-induced IP-formation is mediated by activation of both ETA- and ETB-receptors and does not involve a PTX-sensitive G-protein. ET-induced IP-formation declines during the maturation process; this is associated with a decrease in ET-receptor number and the immunodetectable amount of Gq/11.

Age Factors↗
PubMed1996

Beta-adrenergic receptors in failing human myocardium.

In the human heart the beta-adrenergic receptor-G-protein-adenylyl cyclase system is the most powerful physiologic mechanism to acutely increase contractility and/or heart rate. In the failing human myocardium beta 1-adrenergic receptor number is decreased, and this is accompanied by a reduced beta 1-adrenergic receptor mediated positive inotropic effect. Cardiac beta 2-adrenergic receptor number may or may not decrease; however, beta 2- adrenergic receptor mediated positive inotropic effects are also reduced, possibly because the functional activity of myocardial Gi is increased, thereby inhibiting cyclic AMP formation. The aging human heart shows some similarities with the failing human heart: in both settings, of chronic heart failure and age, beta-adrenergic receptor mediated effects and all other cyclic AMP dependent effects are depressed and Gi-protein is increased.

Aging↗
PubMed1996

In vitro evaluation of N-(fluoro)isopropyl norephedrine as potential cardiac imaging agents for PET.

N-Isopropylnorephedrine (INE) and N-fluoroisopropylnorephedrine (FINE) were found to have a poor affinity for either beta-adrenoceptors and the norepinephrine carrier protein. The low affinity of both compounds for Uptake-1 is probably due to the introduction of a bulky substituent on the nitrogen atom. It is concluded that INE and FINE cannot be used for cardiac imaging with PET.

3-Iodobenzylguanidine↗
PubMed1996

(S,S)- and (S,R)-1'-[18F]fluorocarazolol, ligands for the visualization of pulmonary beta-adrenergic receptors with PET.

The beta-adrenoceptor antagonist carazolol has been labelled with fluorine-18 in the isopropyl group via a reductive alkylation by [18F]-fluoroacetone of the corresponding (S)-desisopropyl compound according to a known procedure. The introduction of fluorine in the isopropyl group creates a new stereogenic centre resulting in the formation of (S,S)- and (S,R)-1'-[18F]fluorocarazolol, which were separated by HPLC. Tissue distribution studies were performed in male Wistar rats. Both the (S,S)- and (S,R)-diastereomers (S.A. 500-2000 Ci/mmol; 18.5-74 TBq/mmol) showed high uptake in lung and heart, which could be blocked by pretreatment of the animals with (+/-)-propranolol. No significant differences were observed between the biodistribution of the two diastereomers. Metabolite analysis showed a rapid appearance of polar metabolites in plasma, while at 60 min postinjection 92% and 82% of the total radioactivity in lung and heart was unmetabolized 1'-[18F]fluorocarazolol. In a PET-study with male Wistar rats, the lungs were clearly visualized and the pulmonary uptake was decreased after pretreatment of the animals with (+/-)-propranolol. The heart could not be visualized. Similar results were obtained in PET-studies with lambs.

Adrenergic beta-Antagonists↗
PubMed1995

Selective downregulation of rat cardiac beta 1-adrenoceptors by cyclosporine A: prevention by diltiazem or angiotensin-converting enzyme inhibitors.

OBJECTIVES: This study attempted to determine whether long-term treatment with cyclosporine A in rats affects cardiac beta 1-adrenoceptors and whether this can be prevented by angiotensin-converting enzyme inhibitors or calcium-entry blocking agents. BACKGROUND: In the transplanted human heart the density of beta 1-adrenoceptors decreases with time after transplantation, whereas that of beta 2-adrenoceptors does not. Because heart transplant recipients are treated with cyclosporine A, we studied whether administration of cyclosporine A in rats might cause this beta 1-adrenoceptor downregulation. METHODS: We performed two studies. First, we treated groups of 10 male normotensive Wistar rats orally with 30 mg/kg body weight per day of cyclosporine A, 10 mg/kg per day of enalapril and 60 mg/kg per day of diltiazem, alone or in combination, for 6 weeks each. Second, we treated groups of 15 male normotensive Wistar rats orally with 15 mg/kg per day of cyclosporine A and 10 mg/kg per day of lisinopril, alone or in combination, for 6 weeks each. At the end of each treatment regimen, cardiac beta-adrenoceptor density and subtype distribution were assessed by (-)-[125I]iodocyanopindolol binding. RESULTS: Both doses of cyclosporine A caused a significant decrease in cardiac beta 1-adrenoceptor density without affecting beta 2-adrenoceptor density. Although diltiazem and the angiotensin-converting enzyme inhibitors alone did not affect cardiac beta-adrenoceptors, they prevented the cyclosporine A-induced downregulation of beta 1-adrenoceptors. CONCLUSIONS: In normotensive Wistar rats, cyclosporine A causes a significant decrease in cardiac beta 1-adrenoceptors without affecting beta 2-adrenoceptors. This can be prevented by diltiazem or angiotensin-converting enzyme inhibitors. In heart transplant recipients, who undergo long-term treatment with cyclosporine A, there is a very similar beta 1-adrenoceptor down-regulation with time after transplantation. Thus, administration of cyclosporine A may cause these beta-adrenoceptor subtype alterations.

Animals↗
PubMed1995

Myocardial and pulmonary uptake of S-1'-[18F]fluorocarazolol in intact rats reflects radioligand binding to beta-adrenoceptors.

The biodistribution of S-(-)-4-(2-hydroxy-3-(1'-[18F]fluoroisopropyl)- aminopropoxy)carbazole ([18F]S-fluorocarazolol, a non-selective beta-adrenoceptor antagonist) was studied in rats (60 min after 18F injection when specific binding in peripheral organs was maximal). 18F uptake in brain, erythrocytes, heart and lung appeared to be linked to beta-adrenoceptors. CGP-20712A and ICI-89,406 inhibited 18F uptake in heart (predominantly beta 1-adrenoceptors) more potently than in lungs (predominantly beta 2-adrenoceptors). In contrast, ICI-118,551 and procaterol were more potent in the lungs than in the heart. ICI-118,551 inhibited 18F uptake in cerebellum (predominantly beta 2-adrenoceptors) more potently than in cerebral cortex (predominantly beta 1-adrenoceptors). Stereoselectivity of the in vivo binding was demonstrated since S-(-)-propranolol inhibited uptake in target tissues more effectively than R-(+)-propranolol. Myocardial and cerebral imaging may be hampered by poor heart-to-lung contrast and low signal-to-noise ratios, but [18F]S-fluorocarazolol seems suitable for positron emission tomography (PET) of pulmonary beta-adrenoceptors.

Adrenergic beta-Antagonists↗
PubMed1995

Dose-dependent separation of dopaminergic and adrenergic effects of epinine in healthy volunteers.

Epinine (N-methyl-dopamine, the active metabolite of ibopamine), is a full agonist at dopamine (DA)-receptors and alpha- and beta-adrenoceptors. To study whether in vivo DA-receptors mediated effects can be separated from alpha- and beta-adrenoceptor effects we compared in 10 male volunteers the effects of i.v. epinine (0.5; 1; 2; 4 micrograms/kg/min for 15 min each) on DA-receptor (changes in serum prolactin)- and alpha- and beta-adrenoceptor (changes in systolic [Psyst] and diastolic blood pressure [Pdiast] and heart rate)-mediated effects with those of dopamine before and after propranolol (5 mg i.v. 45 min pre-infusion), bisoprolol (15 mg p.o. 2 h pre-infusion) and domperidone (10 mg p.o. 1 h pre-infusion). At the 0.5 and 1 microgram doses of dopamine and epinine did not effect Psyst, Pdiast and heart rate but significantly decreased prolactin levels. At the higher dose both dopamine and epinine significantly increased Psyst and heart rate, while only epinine significantly increased Pdiast. In addition, both dopamine and epinine significantly increased diuresis and natriuresis; in contrast, only dopamine, but not epinine dose-dependently increased plasma noradrenaline levels. Domperidone did not affect dopamine- and epinine-evoked blood pressure- and heart rate-changes, but antagonized their prolactin-effects (at least at the lower doses). Bisoprolol and propranolol significantly reduced dopamine-induced Psyst- and heart rate-increases to about the same extent. Propranolol enhanced epinine-induced Psyst- and Pdiast-increases while bisoprolol reduced epinine-evoked Psyst-increase but not Pdiast-increase. Epinine-induced heart rate-increase was abolished by bisoprolol and was converted into heart rate-decrease by propranolol. We concluded that in 0.5 and 1 microgram doses (plasma levels of 20-80 nmol/l)epinine acts only at DA-receptors. Thus, ibopamine in therapeutically recommended doses (3 x 100 mg/day with peak plasma epinine-levels of 50-80 nmol/l) very likely activates only DA-receptors. In higher doses, however, epinine-like dopamine-activates alpha- and beta-adrenoceptors whereby epinine has a stronger alpha-adrenoceptor agonistic activity than dopamine. Moreover, part of the dopamine-effects are indirect via release of endogenous noradrenaline whereas epinine-effects do not appear to include an indirect component.

Adult↗
PubMed1995

PAF effects on eicosanoid release in neonatal rat cardiomyocytes.

The aim of this study was to find out whether, in neonatal rat cardiomyocytes, platelet-activating factor (PAF) can stimulate eicosanoid formation. For this purpose neonatal cardiomyocytes were incubated for 60 min at 37 degrees C in HANKS buffer with PAF (10-1000 nM), and the eicosanoids thromboxane A2 (TXA2) and prostacyclin (PGI2) were assessed in the supernatant as TXB2 and 6-keto-PGF1 alpha, respectively, by an enzyme immunoassay. PAF caused concentration-dependent release of PGI2; TXA2, however, was significantly released only at the highest concentration of PAF (1000 nM). Acetylsalicylic acid (556 microM) and the PAF antagonist WEB 2086 (10 microM) significantly attenuated PAF-induced eicosanoid formation. We conclude that in neonatal rat cardiomyocytes PAF can induce eicosanoid formation and this effect is brought about by activation of a specific PAF receptor.

Animals↗
PubMed1995

Age-dependent changes in the beta-adrenoceptor-G-protein(s)-adenylyl cyclase system in human right atrium.

With increasing age, cardiac beta-adrenoceptor function decreases. To study possible mechanisms underlying this process, we assessed in right atrial appendages from 52 patients of different ages (group A, < 20 years, mean age 3.7 +/- 1.0 years, n = 20; group B, 20-50 years, mean age, 37.9 +/- 2.3 years, n = 9; group C, > 50 years, mean age 66.1 +/- 1.5 years, n = 23) without apparent heart failure who were undergoing open heart surgery beta-adrenoceptor number and subtype distribution (by (-)-[125I]-iodocyanopindolol [ICYP] binding), adenylyl cyclase activity, and Gs- and Gi-protein alpha-subunits (by quantitative Western blotting). beta-Adrenoceptor number in the three groups was not significantly different; in contrast, basal, 10 microM GTP-, 100 microM isoprenaline (ISO), 10 mM NaF-, 100 microM forskolin-, and 10 mM Mn(2+)-stimulated adenylyl cyclase activity was significantly higher in group A than in group B and was further decreased in group C. Similarly, 100 microM terbutaline-, 100 microM histamine-, and 100 microM 5-HT-stimulated adenylyl cyclase activity significantly decreased from group A to group C. Moreover, all these adenylyl cyclase parameters were significantly negatively correlated with the age of the patients. Although Gs alpha was not altered, Gi alpha in group C was significantly higher than in group A; moreover, there was a weak but significant positive correlation between Gi alpha and the age of the patients. We conclude that an impairment of the activity of the catalytic unit of adenylyl cyclase is involved in the decrease in cardiac beta-adrenoceptor function with age; an increase in Gi alpha might contribute further to the reduced beta-adrenoceptor function.

Adenylyl Cyclases↗
PubMed1995

Relation between myocardial beta-adrenoceptor density and hemodynamic and neurohumoral changes in a rat model of chronic myocardial infarction: effects of ibopamine and captopril.

OBJECTIVES: The purpose of this study was to investigate the changes in beta-adrenoceptor density (Bmax) and distribution in a model of chronic myocardial infarction in rats, and to relate possible changes to hemodynamic and neurohumoral abnormalities. In addition, we examined the effects of 8 weeks treatment with ibopamine and captopril. METHODS: There were 3 experiments: (1) Bmax and plasma catecholamines were examined (n = 46), (2) Bmax was compared in infarcted and non-infarcted tissue (n = 13), and (3) contractile function was evaluated by isolated heart perfusion (n = 40). Of rats in Expts. (1) and (3), 50% had myocardial infarction induced by coronary ligation and 50% were controls. Each group was divided between ibopamine, ibopamine and captopril, or standard (no drug) treatment. RESULTS: Bmax was not decreased in rats with myocardial infarction (10.8 +/- 0.8 fmol/mg protein), compared to normal rats (11.4 +/- 0.6 fmol/mg protein), and the ratio beta 1/beta 2 was also unaffected. In infarcted tissue, Bmax was significantly (P = 0.03) lower than in non-infarcted tissue. Baseline left ventricular pressure, systolic and diastolic dP/dT were all impaired (P < 0.001), and plasma norepinephrine levels were elevated in rats with myocardial infarction (16.03 +/- 230 vs. 1287 +/- 83 pg/ml; P < 0.05), compared to normals. Both ibopamine alone and in combination with captopril reduced the elevated plasma norepinephrine levels in infarcted rats (P < 0.001), but only the combination of the 2 drugs significantly increased Bmax in infarcted rats (14.7 +/- 0.8 fmol/mg protein; P = 0.03 vs. untreated myocardial infarction), while ibopamine alone had no significant effect (13.1 +/- 1.1 fmol/mg protein; p = ns). Also, active drug treatment had no significant effect on the hemodynamic changes. CONCLUSIONS: In this coronary artery ligation model of myocardial infarction in rats, no beta-adrenoceptor down-regulation is observed, despite marked abnormalities in baseline left ventricular function and plasma norepinephrine levels. The combination of ibopamine and captopril significantly increases Bmax in infarcted rats, which is accompanied by a reduction in plasma norepinephrine levels, but not by an improvement in hemodynamic parameters.

Adrenergic beta-Agonists↗
PubMed1995

The beta-adrenoceptor subtype(s) mediating adrenaline- and dobutamine-induced blood pressure and heart rate changes in healthy volunteers.

In order to characterize the beta-adrenoceptor subtype(s) mediating blood pressure and heart rate changes induced by adrenaline and dobutamine, we compared the effects in healthy male volunteers of propranolol (5 mg i.v.) and of the beta 1-adrenoceptor selective antagonist bisoprolol (15 mg p.o.) on adrenaline- and dobutamine-infusion induced changes in systolic (P(syst)) and diastolic blood pressure (P(diast)) and heart rate with those on blood pressure and heart rate (HR) changes induced by "pure" alpha- or beta-adrenoceptor agonists (phenylephrine, selective alpha, terbutaline, selective beta 2, isoprenaline, non-selective beta 1 and beta 2). Both beta-adrenoceptor antagonists did not affect phenylephrine (0.25 -1.0 microgram/kg/min for 10 min) infusion induced P(syst)- and P(diast)-increases and HR-decreases. On the other hand, propranolol completely suppressed terbutaline (25-150 ng/kg/min for 15 min) and isoprenaline (3.5-35 ng/kg/min for 8 min) infusion induced P(syst)- and HR-increases and P(diast)-decreases while bisoprolol significantly attenuated only isoprenaline-effects but had nearly no effect on terbutaline effects. Thus, in these doses bisoprolol antagonized only beta 1-adrenoceptor mediated effects, propranolol both beta 1- and beta 2-adrenoceptor mediated effects, but both antagonists had no alpha-adrenoceptor antagonistic effects. Dobutamine (1.0-6.0 micrograms/kg/min for 15 min) infusion significantly increased P(syst), but did not significantly affect P(diast) and HR; bisoprolol markedly reduced dobutamine-induced P(syst)-increase. In the presence of propranolol, however, dobutamine caused P(syst)- and P(diast)-increases and HR-decreases. Adrenaline (20-120 ng/kg/min for 15 min) infusion increased P(syst) and HR and decreased P(diast). Bisoprolol did not affect P(syst)- and HR-increases, but significantly attenuated P(diast)-decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗