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Biomedical subjects

L Lundholm

Publications and source records attributed to L Lundholm.

At least 19 recordsLinked to original sources
PubMed1994

Effect of wall tension on DNA and protein synthesis in bovine mesenteric arteries in vitro.

The aim of this investigation was to study the effect of wall tension and calcium antagonists on DNA and protein synthesis in bovine mesenteric arteries in vitro. The wall tension of the bovine mesenteric arteries was raised by stretching the vessel wall perpendicular to the length axis of the vessel. DNA and protein synthesis were determined by measuring incorporation of 3H-thymidine into DNA and incorporation of 14C-leucine into protein respectively. Elevating the wall tension from 0.05 N to 0.5 N significantly increased 3H-thymidine incorporation and 14C-leucine incorporation after an incubation period of 3 hr. Stretch had no effect on the distribution of 3H-thymidine. The distribution of 14C-leucine was increased by stretch in regular medium and to a less extent in calcium-free medium, which suggest that stretch stimulates the membrane transport of 14C-leucine. When the tension was increased from 0.05 N to 0.5 N for 10 min. before the incubation with 3H-thymidine, no effect was found. One microM nifedipine or felodipine inhibited the increase in 3H-thymidine incorporation caused by stretching, while no effect was found on 14C-leucine incorporation. In calcium-free medium, stretch-induced DNA synthesis was completely abolished. 14C-Leucine incorporation was impaired in calcium-free medium but the stretch-induced increase still remained. The results suggest that mechanical force may play an important role in DNA synthesis and protein metabolism of vascular smooth muscle.

Animals↗
PubMed1989

Relationship between coronary atherosclerosis and "sudden cardiac death". Effects of age and calcium blockers in hypercholesterolemic mini-pigs.

Marked atherosclerosis was produced in the coronary arteries (c.a.) of full-grown ("old") mini-pigs by combination of protracted hypercholesterolemia with two repetitions of irradiation of the heart region. "Sudden cardiac death" with occlusion of some peripheral c.a. occurred to 40% of the pigs within 15 to 21 weeks from the last irradiation. Growing ("young") pigs, after the same treatment, developed more marked atherosclerotic lesions in the c.a. than "old" pigs. There was a trend to a situation in which mortality (58%; p = 0.2) in "young" pigs was higher than in "old". When "old" pigs were treated with the calcium-channel blocker nifedipine (2 x 20 mg/day; mean body weight 66 kg), there was some trend to reduced mortality from 40% to 25% (p = 0.25). If the effects of age and nifedipine were combined, the difference in mortality (58% or 25%) was significant (p less than 0.05). In pigs that had died a "sudden cardiac death", the content of cholesteryl esters in the c.a. rose to values of greater than 60 x 10(-6) mol/g prot. In age-matched control pigs, the mean ester content was 2.8 or 1.2 x 10(-6) mol/g prot. in "young" and "old" pigs. In nonirradiated hypercholesterolemic pigs, the mean ester content in "young" animals was 39 x 10(-6) mol/g prot. but in "old" pigs it came to 4.8 x 10(-6) mol/g prot. 12 months after the "sudden cardiac death" period had ended, the ester content in the surviving pigs was 25 x 10(-6) mol/g prot. in "young" and 3.5 x 10(-6) mol/g prot. in "old" animals. Irradiation had produced some kind of healing effect. This regress in cholesteryl ester content was significantly and moderately delayed by nifedipine treatment. It did not otherwise change the cholesterol metabolism of the arteries. A probable explanation for the partly marked and rapid changes in cholesterol metabolism of c.a. was that there had been a change in phenotype of vascular smooth muscle cells, mainly localised to the intima of the c.a. The vascular endothelial cells influence the phenotype of vascular smooth muscle cells by stimulating proliferation and accumulation of cholesterol by growth factors (PDGF) which act via thrombospondin. By releasing heparin and/or heparin-like glycosaminoglycans, endothelium may inhibit the effect of thrombospondin on vascular smooth muscle cells. An additional contribution is possibly made by cholesterol from high-lipid macrophages.

Animals↗
PubMed1985

Contraction and cyclic AMP-related relaxation of the intimal and medial smooth muscle layers of pig thoracic aorta.

The contractile responses of an alpha-adrenoceptor agonist, phenylephrine, and of histamine were compared in the intimal and medial smooth muscle layers of the pig aortic arch. Further, the relaxant effects evoked by some compounds influencing the cyclic AMP system were compared in the two muscle layers, as well as their effects on the cyclic AMP content and phosphodiesterase activity. Phenylephrine and histamine induced contraction of the smooth muscle layers. The increase in tension was faster in the intimal than in the medial layer. The alpha-adrenoceptor agonist phenylephrine was a more potent contractile agent in the intimal than in the medial smooth muscle. With histamine, no significant difference in the dose-response curves between the two muscle layers was found. Histamine-contracted muscle preparations were relaxed in a dose-dependent manner by the phosphodiesterase-inhibiting compound 3-isobutyl-1-methylaxanthine (MIX) and by 8-bromo-cyclic AMP. The two substances were more potent relaxants in the medial than in the intimal smooth muscle layer. The content of cyclic AMP in the intimal and the medial smooth muscle was increased by MIX. Isoprenaline had no relaxing effect on the muscle preparations and did not change the content of cyclic AMP. There were no differences in the basal levels of cyclic AMP in the intima and media. Vmax of phosphodiesterase activities differed, however, between the two preparations. This study demonstrates that the intimal layer is characterized by a larger contractile responsiveness to phenylephrine and a lower relaxant response to compounds influencing the cyclic AMP-system than those of the medial layer.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Pasteur effect in vascular and intestinal smooth muscle.

The increase in lactate production on changing from aerobic to anaerobic conditions, i.e. the Pasteur effect, has been reported to be small in vascular muscle and especially in aorta. It has been suggested that this may be an artefact caused by damage to the intimal endothelium. We have compared the Pasteur effect in different kinds of pig arteries, but also in rabbit colon. The aerobic lactate production in 60 min was 11-15 mumol/g in the aorta and the carotid artery, but 3 mumol/g in the mesenteric and renal arteries and 4 mumol/g in the rabbit colon. The increase in lactate production under anaerobic conditions was 12-20 mumol/g/60 min in the carotid artery, aorta and rabbit colon and 10 mumol/g/60 min in the mesenteric and renal arteries. When calculated in per cent, the Pasteur effect was greater in the mesenteric artery than in the aorta, but the actual rise in lactate production in mumol/g was higher in the aorta and carotid artery. The high aerobic lactate production of smooth muscle in vitro may be related to its low ability to oxidize glucose; some other substrates may be preferentially oxidized when present in vitro or in vivo.

Adenosine Triphosphate↗
PubMed1984

Sudden death related to advanced coronary atherosclerosis in mini-pigs: influence of some drugs.

Advanced coronary atherosclerosis was produced in 30 mini-pigs by a combination of a hypercholesterolaemic diet and X-irradiation to the precordial region. Within 11-25 weeks after the irradiation, 13 of the 30 animals died a sudden death probably caused by coronary atherosclerosis. The contents of free and ester-bound cholesterol in the right coronary artery were significantly higher in the animals which died spontaneously than in surviving animals. In an untreated group of 12 animals 7 died whereas in a group treated with beta-pyridylcarbinol only 1 out of 5 died. In the coronary arteries, the contents of both free and ester-bound cholesterol were significantly lower in the beta-pyridylcarbinol-treated animals. In a sulfinpyrazone-treated group 3 out of 8, and in a metoprolol-treated group 2 out of 5 animals died. None of these drugs reduced the accumulation of cholesterol in the coronary arteries. The rate of sudden death was 26 +/- 6% (P less than 0.05) lower in the combined group of treated animals than in the untreated ones. By regular ECG recordings, signs which could predict the fatal outcome of the experiment were looked for. Although depressed ST segments were present before death in a few animals, this was not a regular phenomenon. It is concluded that advanced coronary atherosclerosis in mini-pigs often leads to sudden death and that this animal model seems suitable for testing the potential therapeutic effects of drugs.

Animals↗
PubMed1983

Influence of anoxia and dinitrophenol on the phosphorylase a activity and the cyclic nucleotide content of smooth muscle.

The effect of anoxia or 2,4-dinitrophenol (DNP) on the phosphorylase activity and the cyclic AMP and the cyclic GMP content was studied in smooth muscle preparations. When the aerobic conditions were changed to anaerobic in experiments on bovine mesenteric artery, there was a significant increase in the activity of phosphorylase a during the first 60 min. We had observed a reduction of the glycogen content of the artery during this time period, which accounted for about 2/3 of the increase in lactate production (Pasteur effect). Under anaerobic conditions the content of cyclic AMP in the vessel was not changed, and the increase in phosphorylase a activity was not inhibited by a blockade of adrenergic beta-receptors. DNP, which like anoxia inhibits the mitochondrial production of ATP, increased the phosphorylase a activity to the same extent as anoxia. Anoxia and DNP also enhanced the activity of phosphorylase a in pig thoracic aorta and rabbit colon smooth muscle. In thoracic aorta both anoxia and DNP produced a more transient and smaller increase in the phosphorylase a activity than in the mesenteric artery. The Pasteur effect was also relatively smaller (100%) in thoracic aorta than in mesenteric artery (400%). It is suggested that an anoxic increase in the phosphorylase a activity participates in the Pasteur effect in smooth muscle.

2,4-Dinitrophenol↗
PubMed1982

Experimental atherosclerosis in hypercholesterolemic mini-pigs. Regression of cholesterol ester accumulation in aorta and coronary arteries after treatment with clofibrate, beta-pyridylcarbinol or a normo-lipidemic diet.

Studies have been performed on groups of mini-pigs 21-23 months of age, which after 18 months of hypercholesterolemia (approximately 10 mmol) had developed raised atherosclerotic lesions with high levels of cholesterol esters, especially in the abdominal aorta and the coronary arteries. If the hypercholesterolemia was continued for 18 months, no significant change in the cholesterol ester content in the aorta occurred; in the coronary arteries there was a significant decrease in these older pigs. If the hypercholesterolemic pigs also were treated with beta-pyridylcarbinol the findings were very similar to the first. When hypercholesterolemic pigs were treated with clofibrate, or when the hypercholesterolemic diet was replaced with the basal food for 18 months, the plasma cholesterol level was normalized (approximately 2 mmol) within 1-2 months. The cholesterol ester content in the thoracic aorta was reduced in both groups but not that in the abdominal aorta. Clofibrate decreased the cholesterol ester level in the coronary arteries when compared to the hypercholesterolemic group; the drug also reduced the free cholesterol level when compared to the basal group. We suggest that an increased plasma cholesterol level initiated the development of the atherosclerotic lesions; their later development was only partly dependent on the plasma cholesterol level.

Animals↗
PubMed1978

Some properties of Ca-binding microsomal subfractions isolated from rabbit colon muscle.

From a homogenate of rabbit colon smooth muscle a microsomal fraction was isolated, which was divided into subfractions by centrifugation on a discontinuous sucrose gradient. The Ca-binding properties of the subfractions were investigated under different conditions. In the presence of 0.35 mM ATP the Ca binding of the fractions amounted to 4--8 nmol/mg protein. The 35% fraction bound more Ca per mg protein than the 35--45% fraction. The Ca accumulation was comparatively higher both in the presence of 5 mM ATP and in the presence of 5 mM oxalate. The two fractions showed about the same sensitivity for oxalate. This substance stimulated the Ca uptake at 5 mM but not at lower concentrations. The amount and the rate of Ca binding were more dependent on variations in the exogenous ATP concentration in the 35% fraction than was the case for the 35--45% fraction. The Ca binding was completely inhibited by salyrgan when the microsomal fractions were pretreated with this agent. Sodium azide did not influence the Ca-binding capacity of the fractions. It is suggested that the microsomal subfractions of the rabbit colon muscle represent physiologically important parts of the Ca sequestering system of the muscle, since Ca binding takes place at Ca- and ATP-concentrations which are believed to be present in the myoplasm.

Adenosine Triphosphate↗
PubMed1977

Studies on the mechanism of flush induced by nicotinic acid.

Flush is a common side effect of nicotinic acid therapy in patients. The effect is present as long as the level of nicotinic acid increases in the plasma. The mechanism of flush after nicotinic acid has been studied in the ears of guinea-pigs in vivo. The threshold dose of nicotinic acid (1-3 mg/kg) to raise the skin temperature of the ears and to increase the cyclic AMP level of this tissue was similar. Indomethacin and acetylsalicylic acid which inhibit the synthesis of prostaglandins markedly reduce the duration and intensity of the flush. In isolated slices from guinea-pig ears, nicotinic acid increased the level of cyclic AMP; this effect was inhibited by indomethacin. The stimulating action of prostaglandin E1 on the cyclic AMP level of the ear slices was not inhibited by indomethacin. Since administration to man of both cyclic AMP and prostaglandin E1 produces flush it is suggested that nicotinic acid may induce flush by the formation of some prostaglandin which then increases the formation of cyclic AMP.

Animals↗
PubMed1977

Cyclic AMP and Ca-binding in microsomal fractions isolated from rabbit colon smooth muscle.

From a homogenate of rabbit colon muscle two ATP dependent Ca-accumulating microsomal fractions were isolated by differential centrifugation on a sucrose density grandient at 35% and 35-45% sucrose. Adenylate cyclase and phosphodiesterase activities were found in the fractions. The Ca-accumulation and the ATPase activity of these fractions were stimulated by cyclic AMP (10(-5)M) at an ATP concentration of 0.35 mM ATP. In the presence of higher concentrations of ATP (5 mM) cyclic AMP had no effect on the Ca-binding. The higher concentration of ATP markedly increased the cyclic AMP formation in relation to the activity found at the lower concentration of ATP. Isoprenaline (2 X 10(-6)M) stimulated the Ca-accumulation in the 35-45% fraction and increased the hydrolysis of ATP. These effects were absent in the fraction isolated at 35% sucrose. In the former fraction isoprenaline also stimulated the adenylate cyclase activity at 0.35 mM but not at 5 mM ATP. Both the effect of isoprenaline on the Ca-binding and the adenylate cyclase activity were inhibited by the adrenergic beta-receptor blocking agent sotalol. In the 35-45% fraction papaverine (1 X 10(-3)M) stimulated the Ca-accumulation and inhibited the phosphodiesterase activity. It is suggested that cyclic AMP and agents which influence the cyclic AMP metabolism in the microsomes may have a regulatory role on the Ca-binding of the microsomes.

Adenosine Monophosphate↗
PubMed1976

Influence of cyclic nucleotides on protein synthesis in vascular smooth muscle.

The incorporation of leucine-14C into protein in bovine mesenteric arteries was augmented by cyclic GMP (10-3 M) and decreased by cyclic AMP (10-3 M). There was no effect of 5'AMP (10-3 M). The phosphodiesterase inhibiting drugs theophylline (10-3 M) and papaverine (5 x 10-5 g/ml) both decreased the leucine-14C incorporation.

Aminoisobutyric Acids↗