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Biomedical subjects

O E Brodde

Publications and source records attributed to O E Brodde.

At least 19 recordsLinked to original sources
PubMed1992

Uptake of radioligands by rat heart and lung in vivo: CGP 12177 does and CGP 26505 does not reflect binding to beta-adrenoceptors.

The biodistribution of (-)-4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H-benzimidazol-2-one (CGP12177, a non-selective beta-adrenoceptor antagonist) and 1-[2-(3-carbamoyl-4-hydroxy)-(5-3H-phenoxy)]-2-propanol methanesulfonate, (CGP26505, a beta 1-adrenoceptor antagonist) was studied in rats pretreated with various alpha- and beta-adrenoceptor blocking drugs (5 min before 3H injection, in dosages at which the drugs demonstrated the expected selectivity). Cardiac and pulmonary radioactivity were measured after 10 min, when specific binding was maximal. Uptake of [3H]CGP12177 was linked to binding to beta-adrenoceptors since it was not affected by prazosin or yohimbine, and was equally well inhibited by propranolol, unlabelled CGP12177 and isoprenaline. Moreover, atenolol and CGP20712A inhibited [3H]CGP12177 uptake in heart (predominantly beta 1-adrenoceptors) more potently than ICI 118,551, while in lungs (predominantly beta 2-adrenoceptors) ICI 118,551 was more potent than atenolol or CGP20712A. In contrast, [3H]CGP26505 uptake in the target organs was equally effectively inhibited by propranolol and ICI 118,551, and significantly lowered by alpha-adrenoceptor antagonists. We conclude that [11C]CGP12177, but not [11C]CGP2605 will be suitable for positron emission tomography imaging of beta-adrenoceptors in animals.

Adrenergic alpha-Antagonists↗
PubMed1992

Dissociation between phytohaemagglutinin-stimulated generation of inositol phosphates and Ca2+ increase in human mononuclear leucocytes.

We have tested whether phytohaemagglutinin (PHA)-stimulated generation of inositol phosphates (IP) and increases in intracellular Ca2+ can be dissociated in human mononuclear leucocytes. Lowering the incubation temperature from 37 degrees to 25 degrees C decreased PHA-stimulated IP generation by more than 80%, but only marginally affected PHA-stimulated Ca2+ increases. In the absence of extracellular Ca2+, PHA did not stimulate IP generation or Ca2+ increases, although PHA binding to its acceptor sites was not impaired. Increasing extracellular Ca2+ up to 0.15 mM enhanced PHA-stimulated PHA generation but this increase was attenuated by further increasing extracellular Ca2+ to 2.6 mM. Increasing extracellular Ca2+ to 0.3 mM also enhanced PHA-stimulated Ca2+ increases, and further increasing extracellular Ca2+ did not affect it. Co-treatment with 100 microM-prostaglandin E2 completely abolished PHA-stimulated IP generation, but inhibited Ca2+ increases by only 20-30%. These results could be explained by IP-generation-independent Ca2+ increases or by non-linear coupling of IP generation to Ca2+ increases. Since the PHA concentrations required to increase Ca2+ were greater than those required for IP generation, the latter hypothesis can be excluded. Furthermore, the Ca2+ ionophore ionomycin increased intracellular Ca2+ and weakly stimulated IP generation, but with very similar concentration-response relationships. Our data suggest that PHA-stimulated IP generation and Ca2+ increases in human mononuclear leucocytes mainly occur independently of one another rather than sequentially.

Calcium↗
PubMed1992

Receptor systems in the non-failing human heart.

Catecholamines acting through beta 1- and beta 2-adrenoceptors cause positive inotropic and chronotropic effects in the human heart. In recent years, however, evidence has accumulated that in the human heart also other receptor systems can affect heart rate and/or contractility. Positive inotropic effects can be mediated by receptor systems acting through accumulation of intracellular cAMP (Gs-protein coupled receptors such as 5-HT4-like, histamine H2, and vasoactive intestinal peptide) or by receptor systems acting independent of cAMP possibly through the phospholipase C/diacylglycerol/inositol-1,4,5-trisphosphate pathway (such as alpha 1-adrenergic, angiotensin II, and endothelin). In the non-failing human heart, however, activation of all these receptor systems induces only submaximal positive inotropic effects when compared with those caused by beta-adrenoceptor stimulation, indicating that in humans the cardiac beta-adrenoceptor-Gs-protein-adenylate cyclase pathway is the most powerful mechanism to increase heart rate and contractility. On the other hand, at least three receptor systems acting through inhibition of cAMP formation (Gi-protein coupled receptors) exist in the human heart: muscarinic M2-, adenosine A1-, and somatostatin-receptors. Activation of M2- and A1-receptors causes negative inotropic effects in the non-failing human heart: in atria activation of both receptors causes decreases in basal as well as in isoprenaline-stimulated force of contraction, but in ventricles only isoprenaline-stimulated force of contraction is depressed.

Adrenergic beta-Antagonists↗
PubMed1992

Spare receptors for beta-adrenoceptor-mediated positive inotropic effects of catecholamines in the human heart.

We studied whether the human heart has spare receptors for beta-adrenoceptor-mediated positive inotropic effects. Thus, we assessed in right atria and left papillary muscles of patients with different degrees of heart failure under identical experimental conditions affinity (pKI values from (-)-[125I]iodocyanopindolol binding) and potency (pD2 values from contractile responses) for isoprenaline, adrenaline, and noradrenaline in comparison with rat heart. Plots of beta-adrenoceptor occupancy versus responses constructed from these data revealed that rat left atria and papillary muscles had a large receptor reserve for all three beta-adrenoceptor agonists: 50% of maximal response was produced with only 1-3% of beta-adrenoceptor occupancy. In human heart, however, receptor reserve was considerably lower: 50% of maximal response required 8-10% (in right atria) and 20-25% (in left papillary muscles) occupation of beta-adrenoceptors. Receptor reserve declined further with an increasing degree of heart failure (and decreasing beta-adrenoceptor number): in end-stage heart failure (New York Heart Association class IV) both in right atria and left papillary muscles a 1:1 ratio between beta-adrenoceptor occupancy and responses was observed. These data show that the human heart has only a small receptor reserve for beta-adrenoceptor agonists. This may explain why a decrease in beta-adrenoceptor number leads to a decrease in beta-adrenoceptor function early in the development of heart failure.

Adenylyl Cyclases↗
PubMed1992

Terbutaline-induced desensitization of beta 2-adrenoceptor in vivo function in humans: attenuation by ketotifen.

Use of beta-adrenoceptor agonists in long-term treatment of patients with chronic asthma bronchiale or heart failure is of limited value because beta-adrenoceptor desensitization develops. The antiallergic drug ketotifen prevents beta-adrenoceptor agonist-induced desensitization of rat and human pulmonary and lymphocyte beta 2-adrenoceptors. In 10 healthy volunteers in a double-blind, placebo-controlled study, we investigated whether ketotifen also prevents beta-adrenoceptor agonist-induced desensitization of beta 1- and/or beta 2-adrenoceptor-mediated physiologic in vivo effects. beta 1-Adrenoceptor-mediated effects were isoprenaline (ISO) infusion-induced increase in systolic blood pressure (SBP) and bicycle exercise-induced increase in heart rate (HR); beta 2-adrenoceptor-mediated effects were ISO infusion-induced increase in plasma norepinephrine (NE) and decrease in diastolic blood pressure (DBP); ISO infusion-induced increase in HR was assessed as mixed beta 1- and beta 2-adrenoceptor-mediated effect. These parameters were assessed before and after a 14-day treatment with the beta 2-adrenoceptor agonist terbutaline (5 mg three times daily) with or without simultaneous administration of ketotifen (1 mg twice daily). Terbutaline desensitized all in vivo effects involving beta 2-adrenoceptors (ISO-induced decrease in DBP and increase in plasma NE and, to a minor extent, the mixed beta 1- and beta 2-adrenoceptor-mediated increase in HR), but did not affect beta 1-adrenoceptor-mediated in vivo effects; concomitant treatment of the volunteers with ketotifen markedly blunted terbutaline-induced desensitization of beta 2-adrenoceptor in vivo function. We conclude that ketotifen prevents, or at least attenuates, beta-adrenoceptor agonist-induced desensitization of beta 2-adrenoceptor in vivo function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1992

Lack of effect of chronic calcium antagonist treatment on beta 1- and beta 2-adrenoceptors in right atria from patients with or without heart failure.

1. We studied the effects of chronic calcium antagonist (calcium entry blocker, CEB; nifedipine, verapamil, diltiazem) treatment on beta-adrenoceptor density (assessed by (-)-[125I]-iodocyanopindolol [ICYP] binding) and subtype distribution in right atria from 65 patients without apparent heart failure undergoing elective coronary artery bypass grafting (CAD-patients) and from 13 patients with moderate heart failure (NYHA class III to class III-IV) undergoing mitral valve replacement (MVD-patients). 2. In CAD-patients atrial beta-adrenoceptor density was 79.3 +/- 7.9 fmol ICYP bound mg-1 protein (n = 18), the beta 1:beta 2-adrenoceptor ratio 69:31%. Chronic CEB-treatment did not affect either atrial beta-adrenoceptor density or beta 1:beta 2-adrenoceptor ratio. 3. In contrast, in CAD-patients chronically treated with beta 1-adrenoceptor antagonists (atenolol, bisoprolol, metoprolol) and CEB, atrial beta-adrenoceptor density was significantly increased (108.6 +/- 10.5 fmol ICYP bound mg-1 protein, n = 21); this increase was due to a selective increase in beta 1-adrenoceptors. 4. In MVD-patients atrial beta-adrenoceptor density (55.5 +/- 8.7 fmol ICYP bound mg-1 protein, n = 7) was significantly lower (P less than 0.05) than in CAD-patients; beta 1:beta 2-adrenoceptor ratio, however, was not changed (67:33%). Chronic CEB-treatment of MVD-patients did not prevent the decrease in atrial beta-adrenoceptors. 5. We conclude that chronic CEB-treatment does not affect human right atrial beta-adrenoceptor density, either in patients without apparent heart failure or in patients with moderate heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Alpha- and beta-adrenoceptors in hypertension: molecular biology and pharmacological studies.

Recent years have witnessed astonishing progress in our understanding of the molecular basis of adrenoceptor structure, function and regulation and revealed an unexpected heterogeneity of adrenoceptors demonstrating the existence of at least 11 subtypes. This paper discusses the implications of these advances on studies regarding a specific role of adrenoceptors in the development of genetic hypertension. The available data indicate that among the alpha-adrenoceptor subtypes the alpha 2A-adrenoceptor is the most likely candidate for an alteration specifically linked to genetic hypertension in the animal model of the spontaneously hypertensive rat and possibly in some patients. Alterations of other alpha-adrenoceptor subtypes may be specific for some forms of genetic hypertension but are unlikely to play an important role for blood pressure regulation. Most beta-adrenoceptor alterations appear to occur secondary to blood pressure elevation independently of whether hypertension has occurred on a genetic basis or not. Moreover, the mechanisms regulating alpha- and beta-adrenoceptor responsiveness upon prolonged agonist exposure may be altered in hypertension and thereby contribute to the pathophysiology of this disease.

Adrenergic alpha-Antagonists↗
PubMed1992

On the role of renal alpha-adrenergic receptors in spontaneously hypertensive rats.

We tested the hypothesis that a genetically determined increase in renal alpha-adrenergic receptor density might be a pathophysiologically important factor in the spontaneously hypertensive rat model of genetic hypertension. In a first study, we compared renal alpha 1 and alpha 2-adrenergic receptor density with systolic blood pressure in 45 rats of an F2 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids but were unable to detect significant cosegregation between either receptor density or blood pressure. In a second study, we determined renal alpha 1- and alpha 2-adrenergic receptor density in Wistar-Kyoto and spontaneously hypertensive rat kidneys that were transplanted into an F1 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids. Although Wistar-Kyoto kidneys lowered blood pressure in these animals and spontaneously hypertensive rat kidneys increased blood pressure, renal alpha-adrenergic receptor densities were similar in membranes from both types of kidneys. Since rat kidney coexpresses alpha 1A- and alpha 1B-adrenergic receptors, we also investigated whether differential regulation of these two subtypes might conceal ongoing alterations. The alpha 1A/alpha 1B-adrenergic receptor ratio, however, was similar in Wistar-Kyoto rats, spontaneously hypertensive rats, and F1 rats transplanted with a kidney from either strain. Taken together these data do not support the hypothesis that genetically determined alterations of renal alpha-adrenergic receptor numbers play an important role in the development of elevated blood pressure in the spontaneously hypertensive rat.

Animals↗
PubMed1992

Terbutaline-induced downregulation of beta 2-adrenoceptors without Gi-protein alterations in human lymphocytes.

Recent evidence suggests that agonist-induced desensitization of Gs protein-coupled beta-adrenoceptors is accompanied by sensitization of Gi protein-coupled receptors and/or an increase in Gi protein. To find out whether such "cross-regulation" between Gs protein- and Gi protein-coupled receptors can be also demonstrated in vivo in humans, we studied the effects of a 2 week treatment of eight male volunteers with the beta 2-adrenoceptor agonist terbutaline (3 x 5 mg/day) on beta 2-adrenoceptor density and Gi-protein content in lymphocytes and on alpha 2-adrenoceptor density (Gi-coupled receptors) in platelets. Terbutaline decreased the lymphocyte beta 2-adrenoceptor density by about 30%, but had no significant influence on lymphocyte Gi-protein levels (assessed by pertussis toxin-catalyzed [32P]ADP ribosylation) or on platelet alpha 2-adrenoceptor density. We conclude that circulating blood cells are not suitable to demonstrate in humans in vivo a "cross-regulation" between Gs- and Gi-coupled beta- and alpha-adrenoceptors.

Adult↗
PubMed1992

Adrenergic receptors and their signal transduction mechanisms in hypertension.

BACKGROUND: Recent years have witnessed an astonishing proliferation in the number of known adrenoceptor subtypes and related signaling pathways, all of which can potentially be altered in hypertension. Although numerous reports have suggested altered adrenoceptors, guanine nucleotide binding regulatory proteins (G proteins) or effector mechanisms in hypertensive animals or patients, only few clear trends have emerged. CARDIAC AND VASCULAR ADRENOCEPTOR FUNCTION: Cardiac beta-adrenoceptor function is desensitized in various forms of hypertension but it is not clear whether alterations in signaling contribute to this desensitization in addition to the well documented decrease in beta 1-adrenoceptor numbers. Vascular alpha- and beta-adrenoceptor responsiveness are increased and decreased, respectively, in hypertensive animals and patients but the molecular site underlying these alterations has not unequivocally been established. RENAL ADRENOCEPTOR FUNCTION: Renal alpha 1- and alpha 2B-adrenoceptor numbers are frequently increased in genetically hypertensive rats but alpha 1-adrenoceptor-stimulated inositol phosphate formation is unchanged or decreased and alpha 2-adrenoceptor functions remain unclear. Renal beta-adrenoceptor numbers are elevated in many forms of hypertension but it is not clear whether this is accompanied by alterations in receptor function.

Animals↗
PubMed1992

Characterization of the beta adrenoceptor subtype(s) mediating the positive inotropic effects of epinine, dopamine, dobutamine, denopamine and xamoterol in isolated human right atrium.

In patients with chronic heart failure cardiac beta-1 adrenoceptors are reduced, whereas beta-2 adrenoceptor changes vary depending on the etiology of the disease. Beta Adrenoceptor agonists can be used for short-term inotropic support in chronic heart failure; their clinical efficacy might depend on which beta adrenoceptor subtype(s) mediates their positive inotropic effect. Thus, the beta adrenoceptor subtype(s) involved in the positive inotropic effects of clinically used beta adrenoceptor agonists was characterized on isolated electrically driven human right atria by the use of the selective beta-1 adrenoceptor antagonist CGP 20712 A (300 nmol/l) and/or the selective beta-2 adrenoceptor antagonist ICI 118,551 (30 nmol/l). Epinine evoked positive inotropic effects through stimulation of beta-1 and beta-2 adrenoceptors to about the same degree, whereas dobutamine acted mainly at beta-1 adrenoceptors but had a significant beta-2 adrenoceptor component. Both agonists were full agonists causing the same maximum increase in contractile force (Emax) as did isoprenaline or Ca++ (Emax = 1.0). In contrast, denopamine was a partial selective beta-1 adrenoceptor agonist (Emax = 0.75-0.85). Dopamine was in the presence of uptake1-blockade (by 5 mumol/l phenoxybenzamine) a partial agonist (Emax = 0.60-0.70) acting selectively at beta-1 adrenoceptors; in the absence of uptake1-blockade, however, dopamine was a full agonist, indicating that part of its positive inotropic effect is indirect via the release of endogenous noradrenaline. Xamoterol did not exert positive inotropic effects, but concentration-dependently slightly decreased basal force of contraction.

Adrenergic beta-Agonists↗
PubMed1992

[Importance of beta 2-adrenergic receptors in heart failure].

Substantial evidence has accumulated that in the human heart both beta 1- and beta 2-adrenoceptors coexist. As a rule, the amount of beta 2-adrenoceptors is higher in the atria (about 30% of the total beta-adrenoceptor population) than in the ventricular myocardium (about 20%). Both beta 1- and beta 2-adrenoceptors couple to adenylate cyclase and mediate positive inotropic effects of isoprenaline and adrenaline on isolated, electrically driven cardiac preparations. In the atria, stimulation of both beta 1- and beta 2-adrenoceptors causes maximal increases in contractile force; in the ventricular myocardium, however, only beta 1-adrenoceptor stimulation maximally increases contractile force, whereas beta 2-adrenoceptor stimulation evokes only submaximal increases. On the other hand, noradrenaline induces its positive inotropic effect on atrial and ventricular preparations solely via beta 1-adrenoceptor stimulation. Because nordadrenaline is the main transmitter of the human sympathetic nervous system, this indicates that under normal physiological conditions, the heart rate and contractility are under the control of cardiac beta 1-adrenoceptors, whereas cardiac beta 2-adrenoceptors play only a minor role, if at all. However, in situations of stress, when large amounts of adrenaline (acting at both beta 1- and beta 2-adrenoceptors with the same affinity) are released from the adrenal medulla, activation of cardiac beta 2-adrenoceptors may contribute to an additional increase in heart rate and/or contractility. In chronic heart failure, cardiac beta-adrenoceptor function decreases (presumably due to endogenous "downregulation" by the elevated catecholamines) and this decrease is related to the severity of the disease (judged clinically by NYHA functional class).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

Beta-adrenoceptors in the transplanted human heart: unaltered beta-adrenoceptor density, but increased proportion of beta 2-adrenoceptors with increasing posttransplant time.

To study whether in the (denervated) transplanted human heart beta-adrenoceptors are up-regulated we determined in right ventricular endomyocardial biopsies (weighing 2-7 mg) of 8 heart transplant recipients beta-adrenoceptor density and beta 1:beta 2-adrenoceptor ratio in weekly, later monthly intervals for 6-18 posttransplant months. beta-adrenoceptor density was assessed by 1-2 concentration (-)-[125I]-iodocyanopindolol (ICYP, 200 and 150 pmol/l) binding, the beta 1:beta 2-adrenoceptor ratio by a beta 1-adrenoceptor saturating concentration of the selective beta 1-adrenoceptor antagonist CGP 20712 A (500 nmol/l). In biopsies taken from the donor hearts immediately before transplantation beta-adrenoceptor density was 64.5 +/- 6.3 fmol ICYP bound/mg protein (n = 5), the beta 1:beta 2-adrenoceptor ratio 81.2 +/- 2.2:18.8 +/- 2.2%. beta-Adrenoceptor density did not change during the whole period investigated; it was in the first 9 posttransplant weeks 73.1 +/- 8.3 (n = 22) and after 4-18 months 74.2 +/- 7.6 fmol/mg protein (n = 16). In contrast, with increasing posttransplant time beta 1:beta 2-adrenoceptor ratio was shifted towards beta 2-adrenoceptors: in the first 9 weeks it was 80:20% (n = 17), after 16 weeks 75:25% (n = 10) and after 25-80 weeks 65:35% (n = 7). We conclude that in the first 18 posttransplant months beta-adrenoceptors in the transplanted human heart are not up-regulated. There is, however, a gradual decline in beta 1- and increase in beta 2-adrenoceptors with increasing posttransplant time. As noradrenaline acts in the human heart solely at beta 1-adrenoceptors, while adrenaline activates both beta 1- and beta 2-adrenoceptors with about the same potency, with increasing posttransplant time (and increasing proportion of beta 2-adrenoceptors) adrenaline may play an important role for regulation of contractility and/or heart rate in heart transplant recipients.

Adolescent↗
PubMed1991

Development of beta-adrenoceptor number and subtype distribution in the transplanted human heart.

The transplanted human heart is a denervated organ and thus may exhibit beta-adrenoceptor supersensitivity. To monitor possible beta-adrenoceptor changes in the transplanted human heart we assessed, in right ventricular endomyocardial biopsies from eight heart transplant recipients, beta-adrenoceptor number (by (-)-[125I]-iodocyanopindolol [ICYP] binding) and beta 1:beta 2-adrenoceptor ratio (by inhibition of ICYP binding with a beta 1-adrenoceptor saturating concentration of CGP 20712 A, 500 nM) in weekly, later monthly, intervals for 6-18 post-transplant months. In the biopsies of the transplanted hearts, beta-adrenoceptor number was significantly higher than in the right ventricular membranes of the explanted native hearts of the patients; during the whole period, the biopsies' beta-adrenoceptor number was quite stable and no significant increase or decrease was observed. In contrast, with increasing post-transplant time beta 1:beta 2-adrenoceptor ratio was shifted towards beta 2-adrenoceptors: in the first 9 weeks it was 80:20%, while after 4-18 months it had decreased to 66:34%. We conclude that in the first 18 post-transplant months beta-adrenoceptors in the transplanted human heart are not up-regulated. There is, however, a gradual decrease in beta 1- and increase in beta 2-adrenoceptors with increasing post-transplant time. This may have important pathophysiological consequences for regulation of contractility and/or heart rate by endogenous catecholamines in heart transplant recipients.

Adolescent↗
PubMed1991

Pathophysiology of the beta-adrenoceptor system in chronic heart failure: consequences for treatment with agonists, partial agonists or antagonists?

The human heart contains both beta 1-adrenoceptors and a considerable number of beta 2-adrenoceptors, both of which bring about positive inotropic and chronotropic effects of beta-adrenoceptor agonists in vitro and in vivo. In chronic heart failure, the decrease in beta-adrenoceptor function is related to the severity of the disease. However, both cardiac beta 1- and beta 2-adrenoceptors seem to be differentially affected depending on the type of heart failure and its aetiology. beta 1-adrenoceptor function decreases in all forms of chronic heart failure. beta 2-adrenoceptor function, on the other hand, decreases in mitral valve disease, tetralogy of Fallot and end-stage ischaemic cardiomyopathy, and seems to be unaltered (or only mildly uncoupled) in end-stage dilated cardiomyopathy, and possibly in aortic valve disease. Since the human heart has few spare beta-adrenoceptors and these decline with increasing degree of heart failure, beta-adrenoceptor agonists (but only non-selective full agonists) may be of therapeutic use only if the heart needs acute inotropic support; in long-term treatment they may be not effective, since tolerance develops. On the other hand, for long-term treatment selective beta 1-adrenoceptor antagonists may be beneficial since they protect the heart from the deleterious effects of chronic exposure to high (cardiac derived) noradrenaline and simultaneously may restore the previously reduced beta-adrenoceptor function.

Adrenergic beta-Antagonists↗
PubMed1991

Effects of antihypertensive therapy on human alpha- and beta-adrenoceptors.

The present study was designed to investigate the role of plasma catecholamines in the regulation of adrenoceptors in human hypertension. Thirty-three patients with newly detected essential hypertension were treated for 4 weeks with either nifedipine (2 x 20 mg/day), hydergine (2 x 2 mg/day), or both (20 and 2 mg/day, respectively, twice daily each), which lowered blood pressure equally well. Plasma noradrenaline increased during nifedipine, decreased during hydergine and was unaltered during the combination therapy. Lymphocyte beta 2-adrenoceptor density decreased by similar amounts, independent of whether blood pressure was normalized by treatment with nifedipine or hydergine. Platelet alpha 2-adrenoceptor density, however, decreased during nifedipine, slightly increased during hydergine and was unchanged during the combination treatment. We conclude that lymphocyte beta 2-adrenoceptors of hypertensive patients are not regulated primarily by plasma catecholamines but rather by a distinct factor associated with the extent of blood pressure elevation. The density of platelet alpha 2-adrenoceptors, however, appears to be dynamically regulated by catecholamines.

Dihydroergotoxine↗
PubMed1991

Does treatment with beta-adrenoceptor antagonists in vivo alter human adenylate cyclase responsiveness in vitro?

1. Treatment with beta-adrenoceptor antagonists in vivo can alter adenylate cyclase responsiveness in the human heart. We have determined the effects of treatment with four different beta-adrenoceptor antagonists in vivo on the responsiveness of lymphocyte and platelet adenylate cyclase in vitro in healthy volunteers. 2. Propranolol (non-selective, 4 x 40 mg day), bisoprolol (beta 1-selective, 1 x 10 mg day), and ICI 118.551 (beta 2-selective, 3 x 25 mg day) were tested as drugs without and pindolol (non-selective, 2 x 5 mg day) as a drug with intrinsic sympathomimetic activity. Adenylate cyclase stimulation by GTP, prostaglandin E1 and forskolin was determined before, after a 7 day treatment period and 7 days after drug withdrawal. 3. Neither treatment with or withdrawal of any of the beta-adrenoceptor antagonists altered adenylate cyclase responsiveness. 4. We conclude that adenylate cyclase responsiveness in circulating blood cells underlies different regulatory mechanisms than that in solid tissues such as the human heart. Our data suggest that circulating blood cells do not always reflect alterations in solid tissues.

Adenylyl Cyclases↗