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Biomedical subjects

R G Andersson

Publications and source records attributed to R G Andersson.

At least 19 recordsLinked to original sources
PubMed1998

Biphasic response to bradykinin in isolated porcine iliac arteries is mediated by bradykinin B1 and B2 receptors.

Bradykinin-induced responses were studied in isolated porcine iliac arteries. Relaxation was endothelium dependent and seen at low concentrations (10(-10)-10(-8) M) of bradykinin. It was inhibited by the bradykinin B2-receptor antagonist icatibant (HOE-140) and by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine. Bradykinin-induced relaxation was significantly potentiated by the kininase I carboxypeptidase inhibitor mergepta (10(-6) M). Bradykinin (>10(-7) M) elicited contraction of preparations with or without endothelium. The contraction was abolished by indomethacin but was not affected by the thromboxane A2/prostaglandin H2-receptor antagonist SQ 29,548. Icatibant and the bradykinin B1-receptor antagonist desArg9[Leu8]bradykinin significantly decreased bradykinin-induced contraction regardless of endothelial function. The contraction also was decreased by treatment with mergepta. The bradykinin B1-receptor agonist desArg9-bradykinin contracted endothelium-denuded arterial strips. This contraction was significantly decreased by desArg9[Leu8]bradykinin but not by icatibant. The desArg9-bradykinin-induced contraction also was inhibited by the protein-synthesis inhibitor cycloheximide. Neither bradykinin-induced relaxation nor contraction was affected by the ACE inhibitors enalaprilat or cilazaprilat. In conclusion, bradykinin-induced relaxation of isolated porcine iliac arteries was mediated by endothelial bradykinin B2 receptors and mainly nitric oxide. Bradykinin-induced contraction was endothelium independent, indomethacin sensitive, and probably mediated by bradykinin B1 (inducible) and B2 receptors located in the vascular smooth-muscle layer. Kininase I carboxypeptidase, and not ACE, is the main enzyme responsible for bradykinin degradation in these vessels.

3-Mercaptopropionic Acid↗
PubMed1997

Effects of the nitric oxide-donor, GEA 3175, on guinea-pig airways.

This investigation characterized the smooth muscle relaxing effect of a novel nitric oxide (NO)-releasing substance, GEA 3175 (1,2,3,4-oxatriazolium, 3-(3-chloro-2-methylphenyl)-5-[[(4-methylphenyl)sulfonyl]amino], hydroxide inner salt) on guinea-pig trachea. GEA 3175 caused a concentration-dependent relaxation of tracheal smooth muscle precontracted with acetylcholine. This effect was reversed by both okadaic acid, an inhibitor of serine/threonine-specific phosphatases, and iberiotoxin, an inhibitor of Ca2+-activated K+ channels. Furthermore, GEA 3175 had a relaxation potency similar to that of the commonly used NO-donor, S-nitroso-N-acetyl-penicillamine. On the contractile response provoked by electrical field stimulation, GEA 3175 induced a long-lasting relaxation which persisted even after repeated washing. The relaxing effect of GEA 3175 was associated with rises in guanosine 3':5'-cyclic monophosphate (cGMP). In time course studies, cGMP continued to increase with incubation time after stimulation with GEA 3175 and there was a significant elevation of cGMP even after washing. In contrast, incubation with S-nitroso-N-acetyl-penicillamine caused a transient rise in cGMP. The present investigation showed that GEA 3175 evokes long-lasting effects on contractile responses and cGMP levels in guinea-pig trachea. Our results indicate that the relaxing effect of GEA 3175 occurs through a mechanism involving phosphatases and iberiotoxin-sensitive K+ channels.

Acetylcholine↗
PubMed1997

Modulation of P-selectin expression on isolated human platelets by an NO donor assessed by a novel ELISA application.

Adhesion molecules such as P-selectin are potential markers for evaluating platelet activation and studying the role of cell-cell interactions in numerous biological processes related to hemostasis and inflammation. The expression of P-selectin and related molecules has previously been quantified with different techniques. As an alternative to the most common method. flow cytometry, we have developed a useful ELISA method to simultaneously analyse 96 samples for platelet expression of P-selectin. Samples may be stored for at least 7 days at 4 degrees C prior to analysis. The method is simple, reproducible, flexible and requires only standard equipment. Washed platelets (WP) from healthy male volunteers, at a concentration of 1 x 10(7)/microtiter plate well, were stimulated with various known platelet activators and fixed with 0.1% formaldehyde for 10 min. The fixed WP were centrifuged to form a confluent layer in the wells and then incubated with optimal dilutions of primary antibodies (1/2000) directed against P-selectin, CD41, CD9 and secondary antibodies conjugated with alkaline phosphatase. Our results show that P-selectin expression on WP increases significantly upon stimulation with thrombin (0.1-1.0 U/ml), ADP (10 microM) and epinephrine (100 microM). The induction of P-selectin expression by thrombin is fast and has different kinetics depending on the concentration of the agonist. Prior incubation with the nitric oxide donor SNAP (10 microM) inhibits the up-regulation of P-selectin induced by sub-maximal concentrations of thrombin (p < 0.05). This ELISA is suitable for studying the expression and regulation of P-selectin and other surface molecules on human platelets in various pathological states.

Adenosine Diphosphate↗
PubMed1997

Denervation of pigment cells lead to a receptor that is ultrasensitive to melatonin and noradrenaline.

Pigment granule aggregation and dispersal can be studied in the melanophores of isolated scales from the cuckoo wrasse (Labrus ossifagus L.). Stimulation of a melanophore alpha2-adrenoceptor or the sympathetic nerve innervating the cell causes pigment aggregation. When the stimulation ceases, the pigment granules disperse throughout the cell. Studying this migration has been a useful tool in pharmacological research, particularly in investigations of the alpha2-adrenoceptor. Denervation of melanophores creates a receptor that is ultrasensitive to noradrenaline and melatonin. After three to four weeks of isolation, the denervated melanophores exhibit a 10(9)-fold increase in sensitivity. The efficacy of melatonin is increased from a negligible pigment-aggregation ability to the level of a full agonist. The melatonin-induced aggregation can, however, be counteracted by the alpha2-adrenoceptor antagonist yohimbine, but not by alpha1-adrenoceptor antagonist prazosin, indicating that the ultrasensitive receptor possesses alpha2-adrenoceptor features. Consequently, we conclude that the ultrasensitive receptor may represent an alpha2-adrenoceptor that has, due to denervation of the melanophore, become sensitive to melatonin.

Adrenergic alpha-Agonists↗
PubMed1997

Neurokinin A-LI release after antigen challenge in guinea-pig bronchial tubes: influence of histamine and bradykinin.

1. Our aim was to determine if antigen challenge stimulates sensory nerves and provokes the release of tachykinins. The involvement of histamine and bradykinin was studied by using specific receptor antagonists. Capsaicin-induced responses were also examined. Experiments were performed in vitro on tracheal and bronchial preparations from ovalbumin-sensitized guinea-pigs. 2. Characterization of ovalbumin-induced contraction, with regard to histamine and bradykinin, was carried out on airway ring preparations in the presence of phosphoramidon. The histamine H1 receptor antagonist pyrilamine reduced allergen-induced bronchial contractions by about 30%, whereas the bradykinin B2 receptor antagonist icatibant (Hoe 140) did not significantly affect the response. Combined treatment with pyrilamine (1 microM) and icatibant (0.1 microM) reduced the contractions by about 80%, indicating a synergistic inhibitory action. Tracheal preparations were not significantly affected by treatments, neither were capsaicin-induced contractions. 3. To study the outflow of tachykinins, we used a perfused bronchial-tube preparation, allowing simultaneous measurement of smooth muscle tension and mediator release. Neurokinin A-like immunoreactivity (NKA-LI) and substance P-like immunoreactivity (SP-LI) were determined by radioimmunoassay. 4. The results of the perfusion study showed an increased outflow of NKA-LI into the perfusate in response to ovalbumin (127% of basal) challenge. SP-LI determined in some of the samples showed a much lower amount (40 to 70 times lower) of SP-LI than NKA-LI. Treatment with icatibant and pyrilamine, separately and in combination, significantly reduced the ovalbumin-induced NKA-LI outflow by 38%, 26% and 22%, respectively. 5. Capsaicin-induced outflow (124% of basal) was not significantly affected by treatments (icatibant 121%, pyrilamine 107% and combined treatment 111% of basal). However, when pyrilamine was present the increased outflow was not statistically significant. 6. In conclusion, we found that allergen provocation of guinea-pig bronchi caused an increased outflow of NKA-LI that was reduced by treatment with both pyrilamine and icatibant. These findings demonstrate that the allergen-induced release of histamine and bradykinin stimulate sensory nerves and thereby increase outflow of tachykinins that contribute to the allergic reaction.

Animals↗
PubMed1996

Melatonin together with noradrenaline augments contractions of human myometrium.

The hormone melatonin is known to influence the circadian rhythm, and it probably also mediates some of the physiological changes that occur in the body at night. Inasmuch as uterine activity is greater during darkness, we investigated whether melatonin could modulate uterine contractility. Biopsies were performed during caesarean sections to obtain uterine tissue from women who had reached full term. The obtained samples were mounted in organ baths, and spontaneous contractions were recorded. Melatonin alone did not change myometrial contractility, whereas melatonin in combination with noradrenaline potentiated contractions. These results may indicate that melatonin plays a role in the timing of labour, since labour often begins late in the evening.

Dose-Response Relationship, Drug↗
PubMed1996

A melatonin binding site modulates the alpha 2-adrenoceptor.

The melanophores of the cuckoo wrasse (Labrus ossifagus L., a teleost fish) can aggregate and disperse their pigment granules. This migration is controlled by sympathetic nerves and a postsynaptic alpha 2-adrenoceptor. Melatonin was discovered because of its ability to aggregate pigment granules, hence we used the cuckoo wrasse melanophore as a model for studying the effect of melatonin at a cellular level. We found that melatonin had no aggregating effect; instead the hormone enhanced the actions of several alpha 2-agonists, such as noradrenaline, medetomedine and clonidine. When the melanophores were pre-aggregated in vitro by use of the alpha 2-agonist B-HT 920, the aggregation was not augmented after the addition of melatonin. Instead the pre-aggregated granules were dispersed. This suggests that melatonin has affinity for an alpha 2-adrenoceptor site that can modulate the effect of alpha 2-adrenoceptor agonists.

Adrenergic alpha-Agonists↗
PubMed1996

Synergistic inhibition of thrombin-induced platelet aggregation by the novel nitric oxide-donor GEA 3175 and adenosine.

1. The influence of the novel nitric oxide-donor GEA 3175 on thrombin- and ionomycin-stimulated human platelets was investigated. The effect of GEA 3175 was compared with that of adenosine, an activator of platelet adenylyl cyclase. 2. GEA 3175 inhibited thrombin-induced secretion of ATP but did not affect aggregation; similar results were obtained with adenosine. 3. Thrombin-stimulated rises in the cytosolic free Ca2+ concentration, [Ca2+]i, were dose-dependently inhibited by GEA 3175 and adenosine. GEA 3175 and adenosine maximally reduced the initial rise in [Ca2+]i by 41% and 35%, respectively. 4. Simultaneous exposure to GEA 3175 and adenosine nearly abolished both the functional responses (i.e. aggregation and degranulation) and the rises in [Ca2+]i in thrombin-stimulated platelets. 5. Aggregation and increases in [Ca2+]i triggered in platelets by the Ca(2+)-ionophore ionomycin were only marginally affected by a combination of GEA 3175 and adenosine. 6. GEA 3175 potently increased the guanosine 3':5'-cyclic monophosphate (cyclic GMP) content in platelets but did not affect adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels. Adenosine did not increase either the cyclic AMP or the cyclic GMP levels in platelets. However, adenosine and GEA 3175 combined significantly elevated the platelet cyclic AMP content. 7. The results show that simultaneous exposure to GEA 3175 and adenosine promotes potent anti-aggregatory properties in platelets in vitro. The findings suggest that blockage of the cytosolic Ca(2+)-signal, which is probably mediated by an amplified cyclic nucleotide response, is an important event during the synergistic inhibition of thrombin-induced aggregation.

Adenosine↗
PubMed1995

Morphine modulates contractile responses and neurokinin A-LI release elicited by electrical field stimulation or capsaicin in a guinea pig bronchial-tube preparation.

Excitatory nonadrenergic, noncholinergic (e-NANC) bronchoconstrictor responses have been shown to be mediated by the release of tachykinins from sensory nerves. We investigated whether bronchial-tube contractions evoked by electrical-field stimulation (EFS) or capsaicin coincided with the release of neurokinin A (NKA). We also studied the modulatory action of morphine and the ability of naloxone to affect these responses. We used a guinea pig bronchial-tube preparation denuded of epithelium. The method allows simultaneous measurement of smooth-muscle tension and mediator release. A significant release of NKA-LI, at 37.3% above the basal level, was detected in response to EFS. Morphine pretreatment was found to inhibit the release, and such inhibition was not prevented by naloxone. Contractile responses to EFS coincided with the NKA-LI release. Capsaicin stimulation evoked a significant release (35.4%) of NKA-LI, and this release was accompanied by contractions. Treatment with morphine decreased capsaicin-induced responses, and naloxone reversed the inhibitory effect. In conclusion, both capsaicin- and EFS-induced e-NANC responses were inhibited by morphine treatment. This indicates presynaptic inhibition of tachykinin release from sensory nerves. Furthermore, the ability of naloxone to reverse this inhibitory effect differed in capsaicin- and EFS-challenged preparations.

Animals↗
PubMed1995

Pertussis toxin attenuates presynaptic inhibition of cholinergic but not nonadrenergic noncholinergic contraction in guinea pig airways.

Several alpha-2- and opioid receptors exert their intracellular effects via a pertussis toxin-sensitive G protein. Both cholinergic and nonadrenergic noncholinergic nerve-mediated contractions of airways can be reduced by stimulation of presynaptic alpha-2- and opioid receptors. Using guinea pig trachea and bronchi, pretreated with pertussis toxin 100 micrograms/kg or 0.9% NaCl, we investigated whether these inhibitory effects on airway contractions, evoked by electrical field stimulation, are mediated via a pertussis toxin-sensitive G protein. The results indicate a difference between cholinergic and excitatory nonadrenergic non-cholinergic neurotransmission. Inhibition of cholinergic contraction via presynaptic alpha-2- and opioid receptors seems to be mediated via a pertussis toxin-sensitive G protein, whereas inhibition of nonadrenergic noncholinergic contraction is not affected by pertussis toxin.

Animals↗
PubMed1994

Hypoxia induces release of atrial natriuretic peptide in rat atrial tissue: a role for this peptide during low oxygen stress.

A variety of different factors have been shown to induce release of atrial natriuretic peptide from atrial tissue. Among these, stretching of atrial myocytes is considered the most important. In a recent study we showed that atrial natriuretic peptide increased cGMP and reduced lactate accumulation during hypoxia in rat ventricular myocardium. This suggests that atrial natriuretic peptide has a beneficial metabolic effect during hypoxia and raises the question whether hypoxia alone induces release of atrial natriuretic peptide. The right atrium and pieces of the right ventricle, from rats, were incubated in polyethylene vials containing 3 ml Krebs bicarbonate buffer equilibrated with 75% N2 + 20% O2 + 5% CO2 (= hypoxic conditions) or 95% O2 + 5% CO2 (= normoxic conditions). After 10 min, the ventricular tissues and aliquots of the buffer were frozen. Cyclic GMP was analyzed in the ventricular tissue and atrial natriuretic peptide was analyzed in the buffer samples. The results show that the release of atrial natriuretic peptide during hypoxia significantly exceeds the release under normoxic conditions. The hypoxia-induced release of atrial natriuretic peptide over time is characterized by an s-shaped curve with the steepest slope after about 10 min. In the presence of atrial tissue the intracellular level of cGMP in ventricular myocardium increased from 0.3 +/- 0.1 to 2.6 +/- 0.9 pmol/g w wt (P = 0.033, n = 6). We conclude that ANP is released from atrial tissue and induces increased formation of cGMP in ventricular myocardium when oxygen tension is low.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

ACE inhibitors and their influence on inflammation, bronchial reactivity and cough.

Orally active angiotensin converting enzyme (ACE) inhibitors have been successfully used in the treatment of congestive heart failure and hypertension. However, adverse skin reactions, such as angioneurotic oedema have been reported following such medication. Furthermore, these drugs have been associated with a persistent dry cough in subjects without previous known bronchial hyper-reactivity. There is reason to believe that an ACE inhibitor-induced cough is due to an irritant inflammatory state in the airways of susceptible individuals and that this might have pathophysiological features in common with the cough seen as an early symptom of asthma. All inflammatory responses--wheal and flare reactions, airway reactivity, and infiltration by neutrophils and eosinophils--were enhanced by ACE inhibitors in a dose-dependent manner. Other ACE inhibitors might have different proinflammatory profiles.

Adult↗
PubMed1994

Antiatherosclerotic effects of the angiotensin-converting enzyme inhibitors captopril and fosinopril in hypercholesterolemic minipigs.

We evaluated the two angiotensin-converting enzyme (ACE) inhibitors captopril and fosinopril with regard to possible antiatherosclerotic effects in minipigs. Experimental hypercholesterolemia and atherosclerosis was produced in 33 minipigs of the Göttingen strain by an egg yolk/cholesterol-enriched diet for 1 year. One group (n = 11) was fed the atherogenic diet alone and served as a control. A second group (n = 11) received captopril (80 mg/kg/day) added to the atherogenic diet, and a third group (n = 11) was treated in the same manner but with fosinopril (8 mg/kg/day). The drug treatments produced significant reduction in serum ACE activity associated with a reactive increase in plasma renin activity (PRA), but had only minor effects on plasma lipids and lipoproteins. At the end of the treatment period, all animals were killed and examined for degree of atherosclerosis. The percentage of atherosclerotic area in the abdominal aorta was significantly lower in both drug-treated groups as compared with controls. Furthermore, accumulation of cholesterol in the thoracic and abdominal aorta was inhibited by drug treatment. Finally, the percentage of intimal thickening in abdominal aorta was significantly reduced in the drug-treated groups. In conclusion, the ACE inhibitors captopril and fosinopril inhibited development of atherosclerosis in hypercholesterolemic minipigs.

Aldosterone↗
PubMed1994

Protective effect of atrial natriuretic peptide on electrical-field-stimulated rat ventricular strips during hypoxia.

We have previously shown that atrial natriuretic peptide reduces lactate accumulation in non-beating rat ventricular myocardium exposed to hypoxic conditions, and that hypoxia induces release of atrial natriuretic peptide from isolated rat atrial tissue. In these studies we suggested that atrial natriuretic peptide may be physiologically important for protection of the myocardium during periods of oxygen deficit. In the present study, we used isolated strips of rat right ventricle, contracted by electrical-field-stimulation, as a model of a beating myocardium. After contraction stabilization, hypoxic conditions were introduced through aeration with 20% O2, held for 20 or 30 min., and then interrupted by reoxygenation with 95% O2. The contractile force was recorded and the percentage regain of the contractions after reoxygenation was considered as an indication of the amount of cell damage induced during the period of hypoxia. The results show that after 30 min. of hypoxia and subsequent reoxygenation, ventricular strips treated with atrial natriuretic peptide (0.1 microM) recovered 67.9 +/- 2.8% of the prehypoxic force of contraction; control strips from the same ventricle regained 44.9 +/- 4.4% (P = 0.015) of their initial contractile activity. After 20 min. of hypoxia followed by reoxygenation, a ventricular strip incubated together with an atrium regained 78.6 +/- 2.4% of the prehypoxic force of contraction as compared to a 60.2 +/- 2.7% regain (P = 0.002) for the control strip. We conclude that atrial natriuretic peptide protects the working ventricular myocardium during hypoxia, which further supports our previously reported suggestion that the effect on myocardial metabolism is physiologically relevant during situations of oxygen deficit in heart muscle.

Animals↗
PubMed1994

Influence of tolfenamic acid on airway contractility in guinea pigs.

The effect of the NSAIDs tolfenamic acid and indomethacin was tested on acetylcholine-induced and antigen-induced contractions in guinea pig airways. Indomethacin potentiated antigen-induced contractions while tolfenamic acid showed dilatory properties. The effects of the drugs on acetylcholine-induced contractions showed no significant differences; indomethacin had a slightly increasing tendency while tolfenamic acid reduced the contractile response. These results indicate that tolfenamic acid does not have bronchoconstrictive properties, which is a common side effect of other NSAIDs in asthmatics.

Adolescent↗
PubMed1994

Angiotensin converting enzyme inhibitors and atherosclerosis.

This study was designed to evaluate possible antiatherosclerotic effects of angiotensin converting enzyme inhibitors in mini-pigs. Experimental hypercholesterolemia and atherosclerosis were produced in mini-pigs of the Göttingen strain by adding 11% egg yolk and 1% cholesterol to the diet for 52 weeks. The animals were divided into three groups. One group was fed the atherogenic diet alone and served as control. The second group was treated with captopril in a dose of 80 mg/kg/day added to the atherogenic diet on an individual basis. The third group was treated with fosinopril in a dose of 8 mg/kg/day. Both drugs produced a significant reduction in serum ACE activity associated with a reactive rise in plasma renin activity and a slight fall in serum aldosterone concentration. The drug treatment had only minor effects on plasma lipids. The aorta and the carotid and coronary arteries were examined for atherosclerotic lesions. Atherosclerotic plaques developed in the abdominal aorta whereas fatty streaks were present in the thoracic aorta and the coronary arteries. Both drugs significantly reduced the percent visible atherosclerosis in the abdominal aorta. Furthermore, the accumulation of cholesterol in the thoracic and abdominal aorta was significantly reduced. The effect of captopril and fosinopril on endothelium-dependent relaxation of iliac arteries was examined. After addition of 3 x 10(-7) M acetylcholine strips from basal diet fed mini pigs showed a remaining tension of 7.0% +/- 7.1 (p < 0.05 compared to cholesterol-high diet), cholesterol-high diet 36.4% +/- 10.2, captopril 16.9% +/- 4.9 (p < 0.01) and fosinopril 31.7% +/- 4.6 (n.s.). It is concluded that the ACE inhibitors captopril and fosinopril inhibited the development of atherosclerosis in hypercholesterolemic mini-pigs.

Acetylcholine↗
PubMed1993

Local and non-local receptor signalling.

It is suggested that the physiological response caused by an excited membrane-bound receptor can be either local, i.e. localized close to the receptor site, or non-local, spreading over a large volume in the cell. A simple model is presented which shows how locality and non-locality are related to the intrinsic "efficacy" of the drug used in classical receptor theory. It is further demonstrated how the shape of the physiological response versus receptor occupancy is determined by the number of receptor sites which contribute to the physiological response at a given location in the cell.

Animals↗