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Biomedical subjects

R G Andersson

Publications and source records attributed to R G Andersson.

At least 73 records · Page 4Linked to original sources
PubMed1989

Influence of long-term prenalterol treatment on the heart rate and the beta-adrenoceptor binding-sites in rat myocardium.

The density of beta- adrenoceptors has been determined on membranes prepared from rat myocardium. Long-term administration of prenalterol resulted in an increase in the density of receptors, without any change in affinity. The average heart rate increase induced by intravenous prenalterol administration to denervated rats was, however, similar in the prenalterol pretreated and the control groups. We conclude that long-term treatment with a partial beta1-adrenoceptor agonist lead to an increased beta-adrenoceptor density in the myocardium.

Animals↗
PubMed1989

ACE-inhibitor-induced enhancement of spontaneous and IgE-mediated histamine release from mast cells and basophilic leukocytes and the modulatory effect of capsaicin sensitive nerves.

Frequently reported adverse inflammatory skin and airway reactions have been reported in subjects being medicated with angiotensin converting enzyme (ACE)-inhibitors. Intradermally evoked wheal and flare reactions to ovalbumin, capsaicin and bradykinin, in ovalbumin sensitized guinea pigs, was previously demonstrated to be enhanced by pretreatment with the ACE-inhibitor MK 422 (the active parent diacid of enalapril). In vitro results from this study demonstrate that the ACE-inhibitor MK 422 degranulated guinea pig lung and skin mast cells as well as human basophils, and enhanced allergen-evoked histamine release. Local capsaicin pretreatment in vivo of guinea pig skin decreased spontaneous and allergen-triggered release of histamine in vitro from skin mast cells. No clear enhancing effect of MK 422 was seen on the allergen-triggered histamine release in vitro from capsaicin pretreated skin, and the spontaneous release was unaffected by the ACE-inhibitor. The allergen-triggered wheal and flare reaction in ovalbumin sensitized guinea pigs was potentiated by MK 422 and the late phase reaction of the inflammatory response was especially augmented. Capsaicin pretreatment of the guinea pigs abolished this late phase reaction as well as the inflammatory enhancing effect of MK 422. Our in vitro results from capsaicin pretreated skin indicate that the reduced inflammatory response in vivo in capsaicin pretreated skin is due not only to capsaicin induced depletion of neuropeptides from sensory nerves, but also to secondary degranulation of mast cells by one or more of these peptides.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Both the cholinergic and non-cholinergic components of airway excitation are inhibited by morphine in the guinea-pig.

In order to investigate the effect of morphine on the excitatory and inhibitory non-adrenergic, non-cholinergic (NANC) neurotransmission and cholinergic neurotransmission in airways, ring preparations from guinea-pig trachea and bronchi were studied. The preparations were stimulated by electrical field stimulation to elicit contractions and relaxations. Both cholinergic and NANC contractions were reduced by morphine in a dose-dependent way, while the inhibitory NANC neurotransmission was unaffected. A morphine concentration of 10(-4) M reduced the NANC contractions to 20.8 +/- 1.5% of the control contractions and the cholinergic contractions to 49.7 +/- 4.2%. The effect of morphine on cholinergic neurotransmission was completely inhibited by naloxone (10(-5) M) while the effect of morphine on NANC contractions only was reduced to 67.6 +/- 5.6% of the control contractions. It is suggested that morphine influences the excitatory neurotransmission via pre-junctional sites, since morphine had no effect on the acetylcholine-induced contractions.

Animals↗
PubMed1989

Increased bronchial reactivity and potentiated skin responses in hypertensive subjects suffering from coughs during ACE-inhibitor therapy.

The aim of this study was to investigate whether ACE-inhibitors could influence bronchial reactivity and interfere with inflammatory skin responses. Ten hypertensive subjects, who had reacted with coughs during ACE-inhibitor therapy, were treated in a double-blind crossover fashion for two weeks with enalapril and with placebo. Enalapril reduced the PC20 value for histamine and augmented the dermal response. Circulating eosinophilic leukocyte level in venous blood dropped markedly after the histamine bronchoprovocation performed during enalapril treatment. Plasma substance P was reduced after histamine provocation performed during placebo treatment, whereas this reduction was abolished by enalapril. In this study, we have demonstrated ACE-inhibitor-induction of moderately increased bronchial reactivity in subjects with suspected ACE-inhibitor-elicited coughs. It is suggested that coughing during ACE-inhibitor therapy is due to an increased inflammatory state in the airways.

Aged↗
PubMed1989

Differential sensitivity to cAMP among human cord and maternal/adult peripheral lymphocytes discloses differences between PHA- and OKT3-induced activation pathways.

Previous studies have demonstrated that human cord blood lymphocytes are resistant to the anti-proliferative action of prostaglandin E2 (PGE2) in phytohaemagglutinin (PHA)-induced mitogenesis, whereas the same cells activated by OKT3 are at least as sensitive to PGE2 as the corresponding cells from their mothers or other adults. In the present investigation it was found that: (i) PHA-induced proliferation of cord peripheral blood mononuclear leucocytes (PBML) is less sensitive to inhibition by forskolin--a direct activator of adenylate cyclase (AC)--and dibutyryl cAMP--a permeant cAMP analogue--than the proliferation of the corresponding maternal cells; (ii) OKT3-induced proliferation of cord as well as maternal PBML is highly sensitive to inhibition by forskolin and dibutyryl cAMP; (iii) cord PBML show an overall lower rate of AC activity compared with maternal PBML, in response to PGE2 and other autacoids as well as to receptor-independent stimulation; (iv) cord PBML also display a significantly lower rate of degradation of cAMP through cAMP-phosphodiesterase compared with maternal cells; (v) unbroken cord and maternal PBML show comparable rates of cAMP accumulation after stimulation with PGE2. The results suggest a lower sensitivity to the effect of cAMP in cord compared with maternal/adult lymphocytes in PHA-induced proliferation. Moreover, the data illustrate differences between PHA- and OKT3-mediated activation pathways, as well as differences in cell regulation mechanisms between cord and maternal PBML.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Decreased plasma levels of cyclic GMP in patients with chest pain and angiographically normal coronary arteries.

Plasma levels of cyclic nucleotides were determined by radioimmunoassay in patients with (1) angina-like chest pain and normal coronary arteries (suspected spasm angina), (2) exercise-induced angina, and (3) heart diseases other than angina pectoris, as well as in (4) normal subjects. The concentration of cyclic GMP in plasma was significantly lower (by at least three-fold) in patients with suspected spasm angina, as compared with the other groups. No statistically significant difference in the plasma levels of cAMP was observed between the different patient groups. The low cGMP levels in plasma from patients with angina-like chest pain and normal coronary arteries might be an indication of a defect in the vasculature, making it more sensitive to contractile stimuli.

Adult↗
PubMed1988

Glyceryl trinitrate inhibits phosphatidylinositol hydrolysis and protein kinase C activity in bovine mesenteric artery.

The effect of glyceryl trinitrate (GTN) on relaxation, cGMP levels, phosphorylase a activity, phosphatidylinositol hydrolysis and protein kinase C activity was studied on isolated bovine mesenteric arteries (BMA). Two concentrations of GTN were tested, 0.1 nM representing a high affinity component and 1 microM representing a low affinity component of the GTN induced relaxation of BMA, giving a relaxation of 20% and 60% and a 2-fold and 5-fold increase in cGMP, respectively. Phosphatidylinositol hydrolysis and protein kinase C activity were significantly, and to the same extent, reduced at both concentrations tested, whereas the phosphorylase a activity was significantly reduced at the higher concentration only, which might indicate a reduction of the free intracellular Ca2+-concentration at high concentrations of GTN. It is concluded that a therapeutically relevant concentration (0.1 nM) of GTN induces relaxation and an increase in cGMP in bovine mesenteric arteries. The relaxation seems to be associated with an inhibition of phosphatidylinositol hydrolysis and a reduction of the protein kinase C activity.

Animals↗
PubMed1988

Pigment migration in fish erythrophores is controlled by alpha 2-adrenoceptors.

1. The aggregation of erythrosomes within erythrophores of the squirrel fish (Myripristis occidentalis; belonging to the family Holocentridae) was, on pharmacological grounds, shown to be mediated by alpha 2-adrenoceptors. 2. The erythrophores were shown to be controlled by adrenergic nerves activating the alpha 2-adrenoceptors. 3. The erythrophores themselves were found to possess a K+-sensitive mechanism of aggregation. 4. Some similarities and differences of the alpha 2-adrenoceptor-mediated chromatosome aggregation in melanophores and erythrophores are also discussed.

Animals↗
PubMed1988

Early effects of hCG on human testicular cyclic AMP content, protein kinase activity, in-vitro progesterone conversion and the serum concentrations of testosterone and oestradiol.

Ten infertile men underwent testicular biopsy. Cyclic AMP concentration and cAMP-dependent protein kinase activity were determined in biopsies obtained before, and at 3, 10, 20 and 30 min after an intravenous injection of hCG (1500-5000 IU). The in-vitro conversion of progesterone by testicular tissue, and the serum concentrations of testosterone and oestradiol were then studied before and at 30 min after hCG injection. Intravenous injection of hCG induced a rapid increase in cAMP concentration and in the activity of cAMP-dependent protein kinase. The kinetics of this response indicated that cAMP and cAMP-dependent protein kinase mediate hCG effects on the human testis, presumably via effects on the Leydig cells. No stimulatory effect on steroid conversion in vitro or on the serum concentrations of testosterone and oestradiol were seen after 30 min.

Adult↗
PubMed1988

Time course of resensitization of rat uterine beta-adrenoceptor system.

The time course of resensitization of the down-regulated beta-adrenoceptor system of rat myometrium was studied. The isoprenaline-induced decrease of myometrial cAMP reversed rather rapidly and after 4 and 8 days no significant change of the cAMP level was demonstrated, however, the cAMP level was higher than in the control myometrium after 12 days. The elevated phosphodiesterase activity decreased to 80% of control activity after 4 days, but returned to control activity after 8 days. The decreased number of beta-adrenoceptors increased gradually after discontinuing the treatment and reached the number of the controls after 12 days. Our results suggest that the resensitization of the beta-adrenoceptor-cAMP-system is rather complex, the normalization of the cAMP content and the phosphodiesterase activity is more rapid than the normalization of the beta-adrenoceptor number which is a rather slow process in myometrial tissue.

Animals↗
PubMed1988

Relaxation of bovine mesenteric artery induced by glyceryl trinitrate is attenuated by pertussis toxin.

Low concentrations (less than 1 nM) of glyceryl trinitrate (GTN) induced a considerable relaxation of bovine mesenteric arteries (BMA) brought to sustained contraction by the addition of phenylephrine. The concentration-response curve of GTN showed a biphasic pattern with a high and a low affinity component. Pretreatment with pertussis toxin (IAP) attenuated the high affinity relaxant component, but not the low affinity component or the relaxation induced by NaNO2. A polyclonal antibody to IAP counteracted the effect of the toxin on the GTN-response. Low concentrations of GTN increased the cGMP level in BMA via activation of the high affinity pathway. This effect was also inhibited in preparations pretreated with IAP. It is suggested from the present study that GTN induces relaxation of vascular smooth muscle via two separate pathways, the high affinity pathway might involve a receptor-complex interaction with a regulatory protein.

Animals↗
PubMed1988

Effects of an alpha-2 adrenoceptor agonist on angiotensin converting enzyme inhibitor-induced hypotension and potentiated allergen-evoked inflammatory skin responses.

Angiotensin converting enzyme (ACE) inhibitors have been demonstrated to possess proinflammatory properties. Persistent cough and increased broncho-obstruction have been reported frequently in hypertensive subjects on ACE inhibitor therapy. We have studied the effect of an alpha-2 adrenoceptor agonist, clonidine, on MK 422 (active parent diacid of enalapril)-induced hypotension and potentiated inflammatory skin responses in ovalbumin-sensitized guinea pigs. Clonidine was found to abolish dose-dependently MK 422-potentiated ovalbumin-evoked inflammatory dermal responses and it possesses additive hypotensive effects when combined with the ACE inhibitor. It would therefore be interesting to evaluate further alpha-2 adrenoceptor agonists and ACE inhibitors in a combination therapy in humans when single drug antihypertensive therapy of the drugs is insufficient.

Adrenergic alpha-Agonists↗
PubMed1988

Pronounced supersensitivity of postjunctional alpha adrenoceptors after denervation of fish melanophores.

The aggregation of melanosomes within melanophores (pigment cells) attached to isolated scales from the cuckoo wrasse (Labrus ossifagus L.) can be elicited either by stimulation of intrinsic nerves (electrical field stimulation of K+ depolarization) or by adrenoceptor agonists. The melanophores of isolated scales survived in a culture medium for up to 20 days. During this period a progressive increase in sensitivity to exogenously applied noradrenaline took place. After 8 days of isolation there was an about 300-fold increase in sensitivity to noradrenaline. The increased sensitivity was accompanied by a progressive loss of the nerve-elicited response during the first days of isolation. Before and during this early period cocaine was found to potentiate the effect of noradrenaline about 8-fold. On the 3rd day after isolation the effect of cocaine was lost, which coincided fairly well with the time when the nerve-mediated response was lost. The early developing increase in sensitivity to noradrenaline (8-fold) is therefore most likely caused by loss of presynaptic amine uptake, but the main part (50-fold) of the increase in sensitivity presumably has other explanations, like changes in the receptor population.

Adrenergic alpha-Agonists↗
PubMed1987

Potentiation of inflammatory reactions in guinea-pig skin by an angiotensin converting enzyme inhibitor (MK 422).

There have recently been reports of persistent cough and increased broncho-obstruction likely to have been induced by ACE inhibitors. In order to study the effect of MK 422 (the active parent diacid of enalapril) on the inflammatory response, ovalbumin-sensitized guinea-pigs were tested intradermally with ovalbumin, capsaicin and bradykinin. All inflammatory responses were enhanced by treatment with MK 422 for 2 days prior to testing as compared to the responses of control animals. Infiltration of neutrophils, eosinophils, basophils and monocytes was increased following ovalbumin challenge in the MK 422-treated animals. We suggest that skin reactions and airway symptoms noticed during ACE inhibitor therapy might have been due to induced or potentiated inflammatory reactions in the skin or in the bronchial wall.

Allergens↗
PubMed1987

Inhibitory effects of clonidine on allergic reactions in guinea-pig skin.

An experimental guinea-pig model was used to show that clonidine inhibited dose dependently the wheal and flare reaction to i.d. ovalbumin in sensitized animals. The effect of clonidine was counteracted by an alpha 2-adrenoceptor antagonist, yohimbine, but not by an alpha 1-adrenoceptor antagonist, prazosin. An H1-receptor antagonist, clemastine, initially reduced the wheal and flare reaction but did not influence the effect of clonidine. Cimetidine, an H2-receptor antagonist slightly reduced the effect of clonidine on the wheal and flare reaction. It is suggested that clonidine reduces the wheal and flare reaction by stimulating alpha 2-adrenoceptors, which inhibits the axon reflex of the response.

Animals↗
PubMed1987

Effects of enprofylline, a new xanthine derivate, on human pregnant myometrium.

The recently developed xanthine derivate, enprofylline, was studied in an in vitro system with human pregnant myometrium, in particular its effect on spontaneous myometrial contraction, cyclic adenosine monophosphate content, cyclic adenosine monophosphate protein kinase, and cyclic adenosine monophosphate-and cyclic guanosine monophosphate-dependent phosphodiesterase activity. Enprofylline was shown to be a rather potent smooth muscle relaxant [inhibitory concentration that decreases response by 50% (IC50) = 3 X 10(-5) mol/L] and an almost equally potent cyclic adenosine monophosphate-dependent phosphodiesterase inhibitor (IC50 = 10(-4) mol/L), whereas it was a less potent cyclic guanosine monophosphate-dependent phosphodiesterase inhibitor. Enzyme kinetic studies revealed that enprofylline is a competitive cyclic adenosine monophosphate phosphodiesterase inhibitor. Enprofylline increased the cyclic adenosine monophosphate content in a dose-dependent way with subsequent increased activity of cyclic adenosine monophosphate-dependent protein kinase. It is suggested that enprofylline relaxes myometrial smooth muscles and that this is at least partly the result of interference with the cyclic adenosine monophosphate system.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Inhibitory effects of clonidine on the allergen-induced wheal-and-flare reactions in patients with extrinsic asthma.

We investigated the possibility that clonidine, an alpha 2-adrenoceptor agonist, can reduce the wheal-and-flare reactions induced by intradermal injections of allergen in patients with extrinsic asthma. Ten adult subjects with asthma with positive skin tests to one or several pollens were selected. They received, in random order and double-blind manner, clonidine (two doses, each 75 micrograms) or placebo for 3 days, and then, after a 1-week washout period, they crossed over to the other treatment for 3 days. Treatment with clonidine reduced the area of wheal-and-flare reaction induced by allergen without significantly changing the blood pressure or the plasma cortisol level. There was a drop in the histamine content of leukocytes and in the number of eosinophils in peripheral blood after allergen challenge during the placebo treatment, whereas clonidine prevented these changes. The results suggest that treatment with clonidine can reduce the inflammatory reactions induced by allergens in subjects with extrinsic asthma.

Allergens↗