Biomedical subjects

R Bjørnerheim

Publications and source records attributed to R Bjørnerheim.

At least 19 recordsLinked to original sources

PubMed2007

Effects of preload alterations on peak early diastolic mitral annulus velocities evaluated by tissue Doppler echocardiography.

BACKGROUND AND OBJECTIVE: Tissue Doppler echocardiography is proposed to be a relatively preload independent tool for assessment of diastolic function. No data exist on anaesthetized patients in whom myocardial contractility, vascular tone and baroreceptor reflexes are depressed. The aim of this study was to evaluate the effects of preload alterations on tissue velocities in patients during general anaesthesia for coronary arterial bypass surgery. METHODS: Fifteen patients referred for elective aorto-coronary bypass surgery were examined by tissue Doppler echocardiography. Early diastolic velocities in the septal and lateral portion of the mitral annulus were measured during preload interventions induced by tilting of the operating table in patients during general anaesthesia both before surgery and after chest closure. To verify changes in preload we used right atrial pressure and pulmonary artery occlusion pressure. RESULTS: Tissue velocities in both the septal and lateral portion of the mitral annulus were significantly higher when preload was increased, compared to when it was decreased. Alterations in diastolic velocities in the septal portion of the mitral annulus prior to surgery: 0.8 +/- 0.2 cm s-1, P < 0.001, after surgery: 1.1 +/- 0.2 cm s-1, P < 0.001. Alterations in diastolic velocities in the lateral portion of the mitral annulus prior to surgery: 1.4 +/- 0.2 cm s-1, P < 0.001, after surgery: 1.1 +/- 0.3 cm s-1, P < 0.01. Concomitant changes in right atrial pressure and pulmonary artery occlusion pressure were 11 +/- 1 and 12 +/- 1 mmHg before surgery and 13 +/- 1 and 12 +/- 1 mmHg after surgery (P < 0.001 for all), respectively. CONCLUSION: These results show that tissue velocities of the mitral annulus are preload dependent in patients during general anaesthesia both before and after coronary surgery.

Adult↗

PubMed2006

Effects of treatment with a 5-HT4 receptor antagonist in heart failure.

BACKGROUND AND PURPOSE: Positive inotropic responses (PIR) to 5-hydroxytryptamine (5-HT) are induced in the left ventricle (LV) in rats with congestive heart failure (CHF); this is associated with upregulation of the G(s)-coupled 5-HT(4) receptor. We investigated whether chronic 5-HT(4) receptor blockade improved cardiac function in CHF rats. EXPERIMENTAL APPROACH: Rats were given either the 5-HT(4) antagonist SB207266 (0.5 mg kg(-1) 24h(-1); MI(int)) or placebo (MI(pl)) through mini-osmotic pumps for 6 weeks subsequent to induction of post-infarction CHF. In vivo cardiac function and ex vivo responses to isoprenaline or 5-HT were evaluated using echocardiography and isolated LV papillary muscles, respectively. mRNA levels were investigated using real-time quantitative RT-PCR. KEY RESULTS: LV diastolic function improved, with 4.6% lower LV diastolic diameter and 24.2% lower mitral flow deceleration in MI(int) compared to MI(pl). SB207266 reduced LV systolic diameter by 6.1%, heart weight by 10.2% and lung weight by 13.1%. The changes in posterior wall thickening and shortening velocity, cardiac output, LV systolic pressure and (dP/dt)(max), parameters of LV systolic function, did not reach statistical significance. The PIR to isoprenaline (10 microM) increased by 36% and the response to 5-HT (10 microM) decreased by 57% in MI(int) compared to MI(pl). mRNA levels for ANP, 5-HT(4(b)) and 5-HT(2A) receptors, MHCbeta, and the MHCbeta/MHCalpha -ratio were not significantly changed in MI(int) compared to MI(pl). CONCLUSIONS AND IMPLICATIONS: Treatment with SB207266 to some extent improved in vivo cardiac function and ex vivo myocardial function, suggesting a possible beneficial effect of treatment with a 5-HT(4) receptor antagonist in CHF.

Adrenergic beta-Agonists↗

PubMed2005

Defective excitation-contraction coupling in hearts of rats with congestive heart failure.

AIM: We examined the cellular basis for depressed cardiac contractility in rats with congestive heart failure (CHF) secondary to myocardial infarction. METHODS: Six weeks after ligation of the left coronary artery, CHF was confirmed by haemodynamic measures and echocardiographic demonstration of reduced myocardial contractility in vivo. Papillary muscles from CHF animals developed less force than those from sham operated (SHAM) animals. Cell shortening was measured in isolated ventricular myocytes voltage-clamped with high resistance electrodes. Ca2+ transients were measured in fluo-4 loaded myocytes. RESULTS: Contractions triggered by depolarizing test steps from a post conditioning potential of -70 mV were significantly smaller and had significantly reduced velocity of shortening in CHF compared with SHAM myocytes. However, contractions initiated from -40 mV, were similar in amplitude and velocity of shortening in CHF and SHAM cells. L-type Ca2+ current was not significantly different between CHF and SHAM cells, whether activated from -70 or -40 mV. Therefore, in SHAM cells, excitation-contraction coupling exhibited higher gain when contractions were initiated from negative (-70 mV), as compared with depolarized potentials (-40 mV). However, in CHF myocytes, excitation-contraction coupling gain was selectively depressed with steps from -70 mV. This depression of gain in CHF was not accompanied by a significant reduction in sarcoplasmic reticulum Ca2+ content. Isoproterenol increased Ca2+ transients less in CHF than SHAM myocytes. CONCLUSION: In this post-infarction model of CHF, the contractile deficit was voltage dependent and the gain of excitation-contraction coupling was selectively depressed for contractions initiated negative to -40 mV.

Adrenergic beta-Agonists↗

PubMed2001

Natriuretic peptides in patients with aortic stenosis.

BACKGROUND: Whereas atrial natriuretic peptide (ANP) is secreted mainly from cardiac atria, brain natriuretic peptide (BNP) is produced to a larger extent in ventricles. Their relative importance as markers of cardiac function and myocardial hypertrophy is not yet clarified. This study evaluated circulating BNP and ANP and the N-terminal part of their propeptides (NT-proBNP and NT-proANP) as markers of left ventricular hypertrophy and atrial pressure increase in patients with aortic stenosis. METHODS: The plasma concentrations of BNP, NT-proBNP, ANP, and NT-proANP were measured by radioimmunoassay in 67 patients with aortic stenosis. Peptide plasma concentrations were related to measurements obtained by cardiac catheterization and echocardiography. RESULTS: Receiver operating characteristic curves indicated that BNP and NT-proBNP performed best in the detection of increased left ventricular mass and NT-proANP in the detection of increased left atrial pressure. NT-proBNP was significantly increased in mild left ventricular hypertrophy (left ventricular mass index, 78 to 139 g/m(2)), whereas NT-proANP was not increased until left ventricular mass index was 141 to 180 g/m(2). CONCLUSIONS: Plasma BNP and NT-proBNP may serve as early markers of left ventricular hypertrophy, whereas ANP and NT-proANP reflect left atrial pressure increase. The repeated and combined measurements of natriuretic peptides might provide diagnostic information relevant to the evaluation of the stage of aortic stenosis.

Adult↗

PubMed2000

Cyclosporin A inhibits cardiac hypertrophy and enhances cardiac dysfunction during postinfarction failure in rats.

Calcineurin has recently been implicated as a mediator in the signaling pathways that transform intracellular calcium signals to the phenotype of myocardial hypertrophy. The present study was conducted to examine the effects of cyclosporin A (CsA), an inhibitor of calcineurin, on myocardial hypertrophy and remodeling during congestive heart failure (CHF) in rats. After ligation of the left coronary artery, rats were randomized to treatment with CsA or vehicle for 14 days. Compared with vehicle, CsA substantially attenuated myocardial hypertrophy in the CHF rats as assessed by alterations in ventricular weight-to-tibial length ratios (P < 0.05). Myocardial gene expression of skeletal alpha-actin was also reduced in the failing left ventricle (LV) after treatment with CsA (P < 0. 05), although the mRNA levels were still substantially elevated relative to those of sham rats. CsA-induced inhibition of compensatory myocardial hypertrophy in the CHF rats led to increased dilatation of the LV cavity and reduced fractional shortening and peak positive and negative first derivatives of LV pressure (P < 0. 05). Plasma renin and endothelin-1 levels were increased in the CHF-CsA rats, providing humoral cues of aggravated cardiac function. Thus this study supports a crucial role of calcineurin-dependent pathways in the mechanisms of compensatory myocardial hypertrophy during CHF. In addition, our data indicate that inhibition of compensatory myocardial hypertrophy exerts detrimental effects on cardiac remodeling and function after myocardial infarction.

Animals↗

PubMed1999

[Current use of beta-blockers in coronary artery disease].

This article presents the results of a retrospective analysis of the use of beta-blockers and current dosing of these agents in patients with coronary artery disease. While 70 to 78% of patients admitted to Norwegian university hospitals during 1990-1997 for angiographic evaluation of chest pain used beta-blockers, only 43-60% of patients with stable coronary artery disease enrolled in the 4S study in Norway received such treatment. High risk groups such as diabetics and patients with peripheral artery disease were less likely to receive beta-blockers during the early period, but were not treated differentially compared to low risk patients during recent years. Only 15% of patients with congestive heart failure received oral beta-blockers, and only 10.5% intravenous beta-blockade during acute myocardial infarction. The dosing of the most common beta-blockers were low, approximately 50% of doses shown to improve survival after acute myocardial infarction.

Adrenergic beta-Antagonists↗

PubMed1998

[Mortality and morbidity after coronary bypass surgery in high-risk patients].

A total of 113 women and 912 men were submitted to coronary artery bypass surgery at Surgical Department A, Rikshospitalet between August 1982 and December 1986 and followed till January 1993. We found no difference in early mortality, recurrent angina pectoris or non-fatal myocardial infarction in diabetic patients compared to nondiabetic patients. However, total mortality was 1.87 times higher in the diabetic group. For patients with ejection fraction < or = 40%, early mortality was 10.2 times higher than for the reference group. For total mortality we found a practically linear relationship between increased mortality and falling ejection fraction values. We found no relationship between ejection fraction and recurrent angina and non-fatal myocardial infarction, neither did we find any difference in mortality and morbidity between women and men. Although a somewhat higher mortality and morbidity rate must be expected for high-risk patients, they seem to profit to the same extent from the favourable effects of coronary bypass surgery as other patients.

Adult↗

PubMed1997

Hemodynamic characterization of the CarboMedics mitral valve prosthesis.

BACKGROUND AND AIMS OF THE STUDY: The hemodynamic function of the CarboMedics bileaflet mitral valve prosthesis was evaluated by Doppler echocardiography and by heart catheterization. The clinical state of the invasively examined patients was evaluated before and after surgery. METHODS: Doppler echocardiography was performed in 54 patients at six months after surgery. Further, combined right and left heart catheterization was performed in 22 of these patients before surgery and at six months thereafter. RESULTS: The Doppler mean gradients were small (3.6 +/- 1.2 mmHg), and corresponded well with Doppler mean gradients in the subgroup examined with both methods (3.5 +/- 1.1 mmHg) and with the invasive gradients (3.4 +/- 1.9 mmHg); there was also no difference between the different valve sizes. Clinically, pressure recovery distal to the valve is probably so small that no systematic difference between the two techniques of measurement is present. Only physiological regurgitation was found, and no case of valve dysfunction. The patients improved from functional NYHA class 3.1 +/- 0.4 to 1.4 +/- 0.6, regardless of preoperative diagnosis, with most pronounced improvement in those with mitral stenosis. Pulmonary artery pressure was normalized. Pulmonary vascular resistance and cardiac index improved slightly. CONCLUSIONS: In conclusion, the valvular prostheses demonstrated excellent hemodynamic function. There was striking agreement between the small invasive and non-invasive gradients. Finally, the functional status of the patients improved considerably, most distinctly in those patients with prior mitral stenosis.

Adult↗

PubMed1996

[Cardiology education in Norway--does it keep up with the needs?].

Despite an increase in the number of education positions for cardiologists in Norway in the late 1980s, there is felt to be a marked lack of sub-specialists in cardiology in most types of hospitals. A working group under the Norwegian Society of Cardiology has used a questionnaire in 1993, membership data from the Norwegian Society of Cardiology in 1994, a telephone query to all hospitals in the country, and data from the Norwegian Medical Association in 1995 to examine this apparent lack of specialists and the potentials for educating them. We were able to confirm a current lack of approximately 60 cardiologists. In addition, the capacity for education has been reduced and will not compensate for the predicted retirement of specialists from approximately year 2000. The capacity for educating cardiologists must be increased.

Cardiology↗

PubMed1996

Diabetes mellitus and morbidity and mortality risks after coronary artery bypass surgery.

Of 1025 patients (912 men, 113 women) who underwent coronary artery bypass grafting and were followed up for a mean of 7.4 years, 45 (4.4%) had diabetes mellitus. Norwegian population is 1.8-2%). Early mortality was not significantly greater among diabetics than in non-diabetics (2.2 vs. 3.1%, odds ratio--OR-0.44, confidence interval--CI- 0.05-3.56). Diabetic patients had no increased risk of perioperative myocardial infarction (OR = 0.87, CI 0.36-2.10) or of low-output syndrome necessitating intraortic balloon pumping (OR = 0.42, CI 0.55-3.05), and no excess incidence of late non-fatal myocardial infarction (relative risk = 0.69, CI 0.10-1.28) or late chronic heart failure (OR = 2.50, CI 0.5-11.0). Long-term mortality was increased in the diabetic patients (relative risk 1.87, CI 1.60-2.14). Thus diabetes did not entail heightened risk of early mortality, perioperative myocardial infarction or low-output syndrome. Nor was there excess risk of recurrent angina pectoris, late non-fatal myocardial infarction or chronic heart failure among the diabetic patients, but the late mortality risk was increased.

Angina Pectoris↗

PubMed1996

Influence of the exercise protocol on hemodynamic, gas exchange, and neurohumoral responses to exercise in heart transplant recipients.

BACKGROUND: A gradual accommodation to increasing exercise loads has been recommended for exercise testing in denervated posttransplantation heart recipients. However, how the exercise protocol influence the hemodynamic, gas exchange, and hormonal response to exercise in this not been studied. METHODS: Nine heart transplant recipients tests incremental maximal bicycle ergometry tests in random order. Exercise stages of 1 and 3 minute durations were compared with matched work rate increments ranging between 30 and 40 W. Expiratory gas was measured continuously and arterial blood was sampled at each of the matched work rates. RESULTS: Total exercise duration was 6.4 +/- and 15.3 +/- 0.7 minutes for the 1-minute and 3-minute protocols, respectively. Maximal workload was significantly higher during the 1-minute versus the 3-minute protocol (238 +/- 9 versus 200 +/- 11 W, p < 0.001), but maximal oxygen uptake was not significantly different (25.5 +/- 1.1 versus 26.5 +/- 1.2 ml. min-1.kg-1). Hemodynamic, metabolic, and some hormonal parameters showed marked differences between the two protocols, with significantly higher responses observed during the 3-minute protocol for heart rate, ventilation, lactate, atrial natriuretic factor, and growth hormone. Catecholamine (epinephrine and norepinephrine) and insulin responses did not differ between the two tests. If expressed as a relative exercise intensity (percentage of maximal oxygen uptake) no differences in hormonal responses were observed between the two protocols, except for growth hormone response which remained higher during the 3-minute protocol. CONCLUSIONS: Although maximal oxygen uptake was independent of the exercise protocol in these heart transplant recipients, the exercise protocol has a major influence on the hormonal and metabolic response. The delayed response observed for oxygen uptake and hormonal responses suggests a significant physiologic lag time during the more rapidly incremental protocol. These differences should be taken into account when exercise is used as a method to evaluate the heart transplant recipient.

Adult↗

PubMed1995

[Intermittent claudication and beta-blockaders. An unfortunate combination?].

beta-adrenergic blockers have been considered relatively contraindicated in patients with peripheral arterial disease because of reports claiming that these drugs may worsen intermittent claudication. The authors review the published randomized controlled trials and discuss the results of comparisons of this treatment with treatment with alternative drugs. None of the studies of beta-blockade in patients with intermittent claudication showed a reduction of walking distance or impairment of peripheral flow compared with patients given placebo, except one study using a beta-blocker with intrinsic sympathomimetic activity. Alternative drugs are included in only few trials and do not seem to be beneficial. There is a lack of evidence to suggest that beta-blockers adversely effect walking capacity or worsen symptoms in mild to moderate intermittent claudication. beta-blockers should not be avoided if considered in other respects to be the optimal therapy for associated atherosclerotic disease.

Adrenergic beta-Antagonists↗

PubMed1993

Beta-adrenoceptor mediated responses and subtypes of beta-adrenoceptors in cultured rat Sertoli cells.

Membrane particles from Sertoli cell cultures were examined for subtypes of beta-adrenoceptors with a radioligand binding technique using [125I]iodocyanopindolol and a beta 1-selective antagonist (Sandoz 204 545) or a beta 2-selective antagonist (ICI 118 551). Biphasic competition curves and modified Eddie-Hofstee plots revealed a relative distribution of approx. 80% beta 1-adrenoceptors and 20% beta 2-adrenoceptors. Only 45% of the adrenoceptor mediated stimulation of adenylyl cyclase activity was associated with beta 1-adrenoceptors, whereas the remaining 55% was mediated via beta 2-adrenoceptors. The subtype selective antagonists inhibited isoproterenol stimulated aromatization of testosterone to estradiol-17 beta in a concentration-dependent manner. Complete inhibition of beta 1-adrenoceptors resulted in a 45% reduction of estradiol-17 beta formation, whereas similar inhibition of beta 2-adrenoceptors resulted in only a 35% reduction. It is concluded that cAMP-dependent effects of beta-adrenergic agonists in Sertoli cells are mediated by activation of both beta 1- and beta 2-adrenoceptors. The discrepancy between the relative number of beta 1- and beta 2-adrenoceptors and their relative contribution to cAMP production and aromatization indicates that beta 2-adrenoceptors in Sertoli cells are more tightly coupled to the adenylyl cyclase system than beta 1-adrenoceptors. Furthermore, complete inhibition of either beta 1- or beta 2-adrenoceptors by subtype selective antagonists, demonstrates a substantial fraction of spareness between agonist activation of the adenylyl cyclase complex and aromatization.

Adenylyl Cyclases↗

PubMed1991

Effects of chronic amiodarone treatment on human myocardial beta adrenoceptor density and adenylate cyclase response.

STUDY OBJECTIVE: The aim of the study was to evaluate the effect of chronic treatment by amiodarone on beta adrenoceptor density and adenylate cyclase response in human myocardium. DESIGN: Density of beta 1 and beta 2 adrenoceptors was measured by radioligand binding assay. beta Adrenoceptor stimulated production of cAMP was measured by adenylate cyclase assay. EXPERIMENTAL MATERIAL: Right auricular tissue from five patients on chronic amiodarone treatment was compared with that from nine patients in similar clinical and haemodynamic state undergoing coronary bypass surgery. MEASUREMENTS AND MAIN RESULTS: beta 1 and beta 2 adrenoceptor subtypes were quantified using the highly beta 1 selective antagonist Sandoz 204 545. The total beta adrenoceptor density was 28% lower in the amiodarone treated group than in the controls (42.0 v 58.3 fmol.mg-1 protein, p less than 0.02), beta 1 adrenoceptors were 25% lower (33.1 v 44.3 fmol.mg-1 protein, p less than 0.02), and beta 2 adrenoceptors were 36% lower (8.9 v 14.0 fmol.mg-1 protein, p less than 0.02). The cAMP production following non-selective beta adrenoceptor stimulation (isoprenaline 5 mumol.litre-1) was reduced by 38% in the amiodarone treated group (14.2 to 8.7 pmol.min-1.mg-1 protein, p = 0.05). Terbutaline stimulated cAMP production was reduced by 49% (8.3 to 4.3 pmol.min-1.mg-1 protein, p = 0.03). Fluoride stimulated cAMP production was not significantly different (9.4 v 8.4 pmol.min-1.mg-1 protein, p = 0.15). CONCLUSIONS: Chronic treatment with amiodarone is associated with a non-selective downregulation of beta adrenoceptors. beta Adrenoceptor stimulated cAMP production was also reduced. The "beta blocking effect" of amiodarone is probably related to downregulation of beta adrenoceptors.

Adenylyl Cyclases↗

PubMed1991

Specific non-beta-adrenergic binding sites for 125I-iodocyanopindolol in myocardial membrane preparations: a comparative study between human, rat, and porcine hearts.

STUDY OBJECTIVE: The aim was to investigate observed differences in beta adrenergic and apparent non-beta-adrenergic binding of (-)[125I]-iodocyanopindolol (125I-ICYP). DESIGN: Binding parameters for several beta adrenergic agonists and antagonists were examined in radioligand binding assay, using 125I-ICYP as radioligand, in membranes prepared from myocardial tissue. SUBJECTS: Human right auricular myocardium was obtained from patients undergoing open heart surgery. Ventricular myocardium was from Norwegian landrace pigs and Wistar rats. MEASUREMENTS AND MAIN RESULTS: Specific binding of 125I-ICYP was observed. This was only partially competed for with high affinity by isoprenaline, noradrenaline, adrenaline, and atenolol. Considerable interspecies variations in the magnitude of specific non-beta-adrenergic (NBA) binding of 125I-ICYP were shown. The equilibrium constant of dissociation (Kd) of the specific NBA binding sites for 125I-ICYP was 0.3-0.4 nmol.litre-1, and the binding capacities were 20, 106, and 192 fmol.mg-1 protein in rat, human, and porcine myocardium, respectively. The NBA sites were heat sensitive and destroyed by trypsin. Association to NBA sites occurred more rapidly than to beta adrenoceptors. Dissociation of bound 125I-ICYP from NBA sites and beta adrenoceptors at 30 degrees C revealed first order kinetics with t1/2 of 19 min from NBA, as compared to 120 min from beta adrenoceptors. In all three species the ligand specificity for NBA sites was very similar and various adrenergic agonists and antagonists competed with 125I-ICYP binding with the following potencies: timolol greater than propranolol greater than ICI 118 551 greater than pindolol greater than Sandoz 204 545 greater than terbutaline greater than noradrenaline and adrenaline much greater than isoprenaline and atenolol. Of agonists and antagonists for other receptor systems, only the serotoninergic 5-HT2 antagonist ritanserin could displace 125I-ICYP from the NBA sites with relatively high affinity. CONCLUSIONS: 125I-ICYP and several beta adrenoceptor antagonists interact specifically with receptor like proteins other than beta adrenoceptors, and remarkable interspecies difference in the levels of myocardial NBA sites was observed.

Animals↗

PubMed1991

The relationship between atrial pressure, atrial dimensions and atrial natriuretic factor during pacing tachycardia in dogs.

Acute supraventricular tachycardia is known to increase the plasma level of atrial natriuretic factor (ANF). The purpose of these experiments was to investigate if such an increase in plasma-ANF could be ascribed to changes in atrial pressure and atrial dimensions. Eight anaesthetized dogs were instrumented with atrial pressure catheters and sonomicrometers to measure left and right auricular and atrial free wall dimensions. An acute increase in atrial rate from 150 to 200 min-1 for 10 min did not change plasma-ANF or atrial haemodynamic variables. A further increase in atrial rate to 250 or 300 min-1 increased right and left atrial intracavitary pressures (P less than 0.01), both auricular diameters and right atrial free wall segment length (P less than 0.05). Left atrial free wall segment length remained unchanged. Plasma-ANF increased in all dogs (P less than 0.01). The change in plasma-ANF correlated well with changes in atrial pressures as well as with changes in atrial dimensions. These results support the hypothesis that release of ANF during acute atrial tachycardia may in part be attributed to atrial dilatation.

Animals↗

PubMed1991

Hormone-responsive adenylyl cyclase in the human fallopian tube.

Hormone-responsive adenylyl cyclase (AC) activity in biopsies from normal human Fallopian tubes was studied. Enzyme activity with a Km of 0.15 mmol/L and a maximum velocity of 13.8 pmol/mg.min in the basal condition was demonstrated. The addition of prostaglandin E1 (PGE1), PGE2, PGF2a, vasoactive intestinal polypeptide, isoproterenol, and terbutaline increased enzyme activity, with no change in the Km. Maximum stimulation of AC activity was obtained with PGE1, resulting in a 2- to 8-fold increase in AC activity. The response of AC to PGE1 revealed a possible topographical variation, with lowest responses to PGE1 in the isthmus. No such segmental variation in AC activity and response was seen after stimulation with PGF2a, vasoactive intestinal polypeptide, or isoproterenol.

Adenylyl Cyclases↗

PubMed1990

Effects of chronic pindolol treatment on human myocardial beta 1- and beta 2-adrenoceptor function.

To evaluate the effects of chronic pindolol treatment on human myocardial beta-adrenoceptor, membrane preparations from right atrial auricles from patients on chronic pindolol treatment and from patients not treated with beta-blocker were compared with respect to specific binding of [125I]-iodocyanopindolol [( 125I]-ICYP) and adenylate cyclase (AC) activity. Pindolol treatment was associated with a 25% increase in total beta-adrenoceptor density (72.3 vs. 58.3 fmol/mg protein). This increase was due a 40% increase of the beta 1-adrenoceptor subtype (62.2 vs. 44.3 fmol/mg protein), while beta 2-adrenoceptor density was decreased by about 25% (10.0 vs. 14.0 fmol/mg). Isoprenaline 5 mumol/l (9.7 vs. 14.2 pmol/min/mg) and terbutaline 50 mumol/l (4.9 vs. 8.3 pmol/min/mg protein) stimulated adenylate cyclase activity was reduced, whereas fluoride (10 mmol/l) stimulated cAMP production to the same extent in both groups (9.4 vs 9.4 pmol/min/mg protein). Thus, chronic treatment with pindolol was associated with upregulation of the beta 1-adrenoceptors and a down-regulation of the beta 2-adrenoceptors. The total level of beta-adrenoceptors was slightly increased. In spite of this, adenylate cyclase activity and response was reduced.

Adenylyl Cyclases↗