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Biomedical subjects

R G Andersson

Publications and source records attributed to R G Andersson.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1993

Alpha-adrenergic receptors in human myometrium: changes during pregnancy.

Myometrial biopsies from 80 women, delivered by cesarean section in 26-42 completed weeks of pregnancy, were analyzed using radiolabeled alpha 1-antagonist [3H]-prazosin and alpha 2-antagonist [3H]-rauwolscine. Statistical analysis was performed using Student's t test (two-tailed), where p < 0.05 was considered significant. The number of alpha 2-adrenergic receptors did not vary (mean value weeks 37-39 = 17.2 +/- 1.3 fmol/mg protein), while the dissociation constant (Kd) for alpha 2-receptors tended to increase with increasing gestational age, implying reduced affinity near term (p < 0.05, mean values 3.4 +/- 0.2 nM). alpha 1-Receptors, however, increased significantly (p < 0.01) in the pregnancy weeks 37-39 (mean value 29.2 +/- 2.9 fmol/mg prot) while Kd was unaltered. Increased number of alpha 1-receptors, along with a decreased affinity of alpha 2-receptors, could, in combination with other factors, play a role in the initiation of labor.

Analysis of Variance↗
PubMed1992

Relationship between histamine, lipoxygenase and cyclooxygenase products in antigen-induced contraction in guinea-pig tracheal tube preparations.

We have used a tracheal tube preparation to study antigen-induced contraction in sensitized guinea pig airways. Treatment with both the cyclooxygenase inhibitor indomethacin and the lipoxygenase inhibitor MK-886 (L-663,536) affected this contraction in preparations with intact epithelium. Indomethacin potentiated and MK-886 inhibited part of the contraction. Leukotriene release from tracheal tubes was measured after antigen challenge, and was found to be significant in preparations with an intact epithelium. When the epithelium was removed, the histamine receptor antagonist mepyramine reduced antigen-induced contraction by 90%. Our results show that when the epithelium is absent, histamine is the most important mediator in the contraction. With the epithelium left intact, the contraction is more complex: both the cyclooxygenase and lipoxygenase pathways are involved, and our findings indicate that eicosanoid production is associated with the airway epithelium.

Animals↗
PubMed1992

The modulatory effects of prostaglandins on both excitatory and inhibitory non-adrenergic non-cholinergic neurotransmission in guinea-pig airways.

Guinea-pig trachea and bronchi were used to investigate the effects of indomethacin and prostaglandin E2 (PGE2) on non-adrenergic non-cholinergic excitatory (e-NANC) and inhibitory (i-NANC) neurotransmission evoked by electrical field stimulation. Indomethacin potentiated e-NANC responses in bronchi with intact epithelium but had no effect on epithelium-denuded preparations. Inhibitory NANC responses were increased by indomethacin independent of the epithelium. Both i-NANC and e-NANC neurotransmission were suppressed by PGE2 in a dose-dependent manner. These results indicate that endogenous prostaglandins (e.g. PGE2) generated from the epithelium have an inhibitory effect on i-NANC and e-NANC nerve responses in airways. The epithelium is presumably not the only source for generation of prostaglandins that are involved in i-NANC neurotransmission.

Acetylcholine↗
PubMed1992

Epithelial modulation of allergen and drug effects in guinea pig airways.

The effect of egg albumin (EA) challenge on tracheal tube preparations from sensitized guinea pigs was studied with regard to EA permeability, histamine release and penetrability, and the contractile response of the preparation. We used a plethysmographic method that allowed simultaneous measurement of changes in smooth muscle tension and collection of samples for determination of mediators. Our results clearly show that epithelial damage potentiates the contractile response to histamine, potassium ions, and acetylcholine. Epithelial damage did not alter the maximal contractile response in preparations challenged with high antigen concentrations (EA, 1 mg/ml), but histamine release measured in the perfusate increased substantially. The permeability of the preparations to EA was greater when the epithelium was damaged. No increase in the permeability in response to the EA challenge was observed. The present study has demonstrated that guinea pig airway epithelium constitutes a barrier for both antigen and drugs. We also present a method for recording contractile responses from intact whole tracheal preparations, in which the epithelium can still act as a barrier, as is the case in vivo.

Allergens↗
PubMed1992

In vivo microdialysis estimation of histamine in human skin.

Microdialysis, a new bioanalytical sampling technique, enables the measurement of substances in the extracellular space. This study investigates the use of the technique in the in vivo measurement of histamine levels in human skin. Microdialysis probes are equipped at the tip with a semipermeable polycarbonate membrane which permits the passive diffusion of substances. 16 probes were inserted, via a guide, into the skin of the ventral forearm of 8 patients or volunteers. The probe was perfused at a flow of 5 microliters/min, with samples being collected at intervals of 10 min and analysed by RIA technique. The mean histamine level in the first 10-min sample following probe insertion was 39.4 nM. The mean histamine value fell with successive 10-min samples (8.8, 4.6, 2.3 nM). An equilibration period of 40 min following probe insertion is suggested for histamine studies, where provocation of the skin is to be performed. Microdialysis appears to be a promising new tool for quantitative and chronological studies of cutaneous inflammatory mediators.

Dialysis↗
PubMed1991

The melanophore aggregating response of isolated fish scales: a very rapid and sensitive diagnosis of whooping cough.

Pertussis toxin (PT) has been found to block noradrenaline-induced pigment aggregation in fish melanophores, and, based on this, a rapid and highly sensitive assay for PT was developed. Some preliminary results have also indicated that it may be possible to detect PT-like activity in saliva samples from patients with clinically suspected pertussis. In the present study the diagnostic value of the fish melanophore method was evaluated in 70 patients suspected of having pertussis; culture, serology and physician diagnosis were used as reference methods. In 60 of the patients, pertussis was verified by at least one of the reference methods. The melanophore test showed PT-like activity in saliva samples from 58 of the patients. Three patients with reference-verified pertussis showed no PT-like activity in the test; among these, one patient had been immunized and had also been treated with erythromycin during 3 days immediately prior to visiting the hospital. The melanophore test has three major advantages: it allows detection of pertussis in the early and curable stage of the disease; it takes only 2 h to perform; and it requires no sophisticated equipment.

Adolescent↗
PubMed1991

Enalaprilat versus cilazaprilat: a comparison of allergic skin reactions in the guinea pig.

ACE-inhibitors have for some time been used in the treatment of hypertension. Apart from inhibiting the conversion of angiotensin I to II, the drugs also affect the metabolism of some inflammatory agents, like bradykinin and substance P. Egg albumin (EA)-sensitized guinea pigs were pretreated with the ACE-inhibitors. Measurement of flare and wheal areas induced by an intradermal injection of EA, showed that enalaprilat significantly increased, whereas cilazaprilat slightly decreased, the reaction area. Enalaprilat also showed an enhancement in histamine and substance P (SP) contents in the skin. In vitro incubation of guinea pig biopsies with enalaprilat potentiated EA- but not SP-induced histamine release. The EA-induced effect was abolished if the animals were pretreated with capsaicin. The conclusion is that cilazaprilat, in contrast to enalaprilat, does not potentiate inflammatory reactions in the guinea pig.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Is the airway epithelium responsible for histamine metabolism in the trachea of guinea pigs?

The aim of the study was to investigate whether or not the epithelium plays an active role in histamine metabolism, via the histaminase and/or methyltransferase pathways. Isolated tracheas from guinea pigs sensitized to egg albumin (EA) were used. The epithelium was either left intact or removed from the preparations. The tracheal tubes were mounted in a chamber, allowing estimation of smooth muscle tension, and perfused with buffer. In some experiments the perfusate was collected for determination of histamine and methylhistamine. Mepyramine was used to evaluate the contribution of histamine to the EA-induced contraction. Mepyramine reduced the contraction by 90% when the epithelium was removed; with intact epithelium the reduction was 47%. Aminoguanidine, a histaminase inhibitor, significantly potentiated the response to EA when the epithelium was left intact. Traces of methylhistamine were detected in tissue extracts and perfusates. We conclude that histaminase is present in the preparation and that it can contribute to the inhibitory effect of the epithelium by means of histamine degradation.

Amine Oxidase (Copper-Containing)↗
PubMed1991

MCH-induced pigment aggregation in teleost melanophores is associated with a cAMP reduction.

It has previously been shown that alpha 2-adrenoceptors are involved in noradrenaline-induced pigment aggregation within fish melanophores. In the present investigation, melanin concentrating hormone (MCH) elicited pigment aggregation (EC50 approximately 1 x 10(-7) M) that was associated with a significant reduction in the cAMP content; 1 x 10(-7) M MCH reduced the cAMP content from a basal level of 50.4 +/- 2.8 pmol/mg protein to 36.9 +/- 3.8 pmol/mg protein. Like the alpha 2-adrenoceptor-induced pigment aggregation, the MCH response was effectively blocked by the adenylate cyclase stimulator forskolin. These findings suggest that attenuation of cAMP may serve as an intracellular signal transduction mechanism for both MCH and noradrenaline.

Animals↗