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L L Aarhus

Publications and source records attributed to L L Aarhus.

36 records · Page 2Linked to original sources
PubMed1990

Indomethacin improves the impaired endothelium-dependent relaxations in small mesenteric arteries of the spontaneously hypertensive rat.

Impairment of endothelium-dependent relaxations may be of primary importance in hypertension, if this impairment were to occur in resistance arteries. Therefore, endothelium-dependent relaxations to acetylcholine were studied in the mesenteric resistance vessels of spontaneously hypertensive and Wistar-Kyoto rats. Rings with and without endothelium were suspended in a myograph filled with physiological salt solution at 37 degrees C and aerated with 95% O2/5% CO2; the isometric tension was recorded. Acetylcholine caused relaxations only in rings with endothelium. In the spontaneously hypertensive rat, relaxations were impaired and markedly biphasic with an early rapid relaxation followed by a secondary contraction. Indomethacin inhibited the secondary response and augmented the duration of the relaxations induced by acetylcholine in the arteries from spontaneously hypertensive rats. These findings suggest that the decreased endothelium-dependent relaxation to acetylcholine in mesenteric resistance vessels of the spontaneously hypertensive rat is due to the release of a constrictor prostanoid which partly offsets the response of the vascular smooth muscle to endothelium-derived relaxing factor(s).

Acetylcholine↗
PubMed1989

Pharmacology of pentoxifylline in isolated canine arteries and veins.

Pentoxifylline possesses vasodilator properties, but little information is available on the mechanism of action explaining this vasodilator effect. The present experiments were designed to determine the effects of the compound on vascular smooth muscle, endothelium, and adrenergic nerves in rings of isolated canine blood vessels. Pentoxifylline did not affect basal tension in coronary and femoral arteries or in saphenous and mesenteric veins; it did not alter the rhythmic activity of the latter, but did cause endothelium-independent relaxations of unstimulated basilar arteries. In coronary arteries and saphenous veins, but not femoral arteries contracted with prostaglandin F2 alpha, the compound caused relaxations which were not affected by propranolol or by removal of the endothelium. Pentoxifylline inhibited the endothelium-dependent contractions to the Ca2(+)-ionophore A23187 in the basilar artery. In saphenous veins (with endothelium), pentoxifylline did not inhibit responses to high K+, electrical stimulation of the adrenergic nerves, or exogenous norepinephrine (NE); it reduced contractions evoked by xylazine and hypoxia. In the basilar artery and the saphenous vein, the inhibitory effect of pentoxifylline was prevented by inhibitors of cyclooxygenase and thromboxane synthetase. These experiments suggest that the dilator properties of pentoxifylline in isolated canine blood vessels are primarily at the level of the vascular smooth muscle and may involve decreased production of, or reduced responsiveness to, endogenous thromboxanes.

Animals↗
PubMed1989

Failure of atrial natriuretic factor to increase with volume expansion in acute and chronic congestive heart failure in the dog.

It remains unclear whether the levels of atrial natriuretic factor (ANF) observed in chronic CHF are appropriate for the magnitude of elevations in atrial pressures. Specifically, it is not known whether acute increases in atrial pressure in CHF can result in further significant increases in circulating ANF. The present study was designed to test the hypothesis that in chronic CHF there is an attenuated relation between circulating ANF and atrial pressure such that the heart is unable to respond to further increases in atrial pressure with appropriate increases in ANF. Cardiovascular hemodynamics and plasma levels of ANF were measured at baseline and after rapid right ventricular pacing (RRVP) to produce acute (n = 10, 25 minutes RRVP) and chronic (n = 7, 14-16 days RRVP) CHF. Acute saline volume expansion was then performed in each group to determine the response of circulating ANF to acute increases in atrial pressure in both acute and chronic CHF. In chronic CHF, right atrial pressure was much higher than in acute CHF (8.5 +/- 0.9 vs. 3.4 +/- 1.3 mm Hg, p less than 0.05); however, circulating ANF was not greater in chronic as compared with acute CHF (385 +/- 73 vs. 500 +/- 89 pg/ml), which is consistent with an attenuated release of ANF in chronic CHF. In response to volume expansion, right atrial pressure increased in both acute (3.4 +/- 1.3 to 12.1 +/- 7 mm Hg) and chronic (8.5 +/- .9 to 13.3 +/- 1.0 mm Hg) CHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Dietary omega 3 polyunsaturated fatty acids augment endothelium-dependent relaxation to bradykinin in coronary microvessels of the pig.

1. The effects of chronic dietary supplementation with omega 3 polyunsaturated fatty acids on endothelium-dependent relaxations were examined in isolated coronary microvessels of the pig. 2. Animals were maintained for four weeks with or without dietary supplementation of purified eicosapentaenoic acid (3.5 g daily) and docosahexaenoic acid (1.5 g daily). Fatty acid profiles of plasma lipids showed that only the fraction of eicosapentaenoic acid increased by the treatment, together with a decrease of that of arachidonic acid. 3. In the treated group, endothelium-dependent relaxations to bradykinin were significantly augmented, while contractions to acetylcholine or relaxations to nitroprusside were unaltered. 4. These results indicate that dietary omega 3 polyunsaturated fatty acids (mainly eicosapentaenoic acid) augment endothelium-dependent relaxations in coronary microvessels of the pig, without changing the ability of vascular smooth muscle to contract or relax.

Animals↗
PubMed1988

The effect of cold on adrenergic neurotransmission in canine saphenous arteries and veins.

The effect of severe cold (5 to 10 degrees C) on adrenergic neurotransmission was compared in the isolated cutaneous (saphenous) artery and vein of the dog. The vein contracted to sympathetic nerve stimulation at temperatures as low as 10 degrees C; higher temperatures were needed for the artery to contract. Both blood vessels contracted to exogenous norepinephrine at temperatures as low as 5 degrees C. However, the contractile response to exogenous norepinephrine was less in the saphenous artery, and contractions to high K+ solution were depressed by cooling more in the artery than in the vein. During electrical stimulation of the sympathetic nerves in saphenous arteries and veins previously incubated with labeled norepinephrine, progressive cooling from 37 to 5 degrees C caused a sharp decline in overflow of [3H]norepinephrine and its metabolites. However, overflow of labeled norepinephrine in both blood vessels continued at very cold temperatures. Thus the inability of the saphenous artery to contract to sympathetic nerve stimulation at 10 degrees C can be explained by a greater sensitivity of the arterial smooth muscle to the direct depressant effect of cold, rather than to a differential release or metabolism or norepinephrine in the arterial wall or a loss of responsiveness to norepinephrine at very cold temperatures.

Animals↗
PubMed1987

Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin.

To test the ability of regenerated endothelium to evoke endothelium-dependent relaxations, male Yorkshire pigs underwent balloon endothelial denudation of the proximal left anterior descending coronary artery. Endothelium-dependent responses were examined in vitro, in rings of coronary segments taken from the denuded area or from the proximal left circumflex coronary artery. The experiments were performed 8 days or 4 weeks after the denudation. Endothelial regrowth was confirmed by histologic examination 8 days after the denudation and by demonstrating the presence of endothelium-dependent relaxations to bradykinin; at that time aggregating platelets evoked normal endothelium-dependent responses. However, 4 weeks after the denudation, the relaxations to aggregating platelets were markedly depressed although continuous endothelial lining was present, and the endothelium-dependent responses to bradykinin, adenosine diphosphate, the Ca2+-ionophore A23187, platelet activating factor, and thrombin were unaltered. Four weeks after denudation, endothelium-dependent relaxations to serotonin were depressed. Higher concentration of serotonin induced endothelium-dependent contractions in quiescent rings with regenerated endothelium, suggesting that regenerated endothelial cells may produce endothelium-derived constricting factor(s) and release less endothelium-derived relaxing factor(s) when exposed to the monoamine. The endothelium-dependent relaxation to serotonin was not reduced by the S2-serotonergic antagonist ketanserin but prevented by the combined S1- and S2-serotonergic blocker methiothepin. The platelet-induced relaxation was due to released serotonin and adenine nucleotides in control left circumflex coronary arteries, but in left anterior descending coronary artery with regenerated endothelium, it was due solely to the latter. The platelet-induced contractions were due to activation of receptors on the smooth muscle cells. Four weeks after denudation, regenerated endothelial cells were morphologically different from native cells; they were elongated and cuboidal, and the number of the cells had increased twofold. At this state, eccentric myointimal thickening was present in the previously denuded portion. These experiments indicate that the protective role of endothelial cells against the vasoconstriction induced by aggregating platelets is depressed in the chronic regenerated state. A lack of responsiveness to serotonin appears to be the cause for the endothelial dysfunction.

Adenosine Diphosphate↗
PubMed1987

Denervation augments alpha-2 but not alpha-1 adrenergic responses in canine saphenous veins.

Experiments were performed in order to determine the influence of sympathetic denervation on alpha-1 and alpha-2 adrenergic responses in canine saphenous veins. In female dogs anesthetized with sodium pentobarbital, the left lumbar sympathetic chain was excised from L1 to L7. After a 3- to 5-week period, the left (denervated) and right (innervated) saphenous veins were removed, cut into rings and suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Denervation reduced significantly the norepinephrine content of the venous rings and the contractile responses evoked by the indirect sympathomimetic amine, tyramine. The contractile responses evoked by exogenous norepinephrine were augmented by denervation under control conditions (16.7-fold shift in concentration-effect curve) and also after inhibition of neuronal and extraneuronal uptake and beta adrenoceptors (3.8-fold shift in curve). Denervation increased the contractile responses evoked by the alpha-2 adrenergic agonist, UK 14,304 (5-fold shift in concentration-effect curve), but not those produced by the alpha-1 adrenergic agonist, phenylephrine. The selective augmentation of alpha-2 adrenergic responses by denervation may reflect the preferential innervation of alpha-2 adrenoceptors in the canine saphenous vein.

Animals↗
PubMed1986

Modulation of endothelium-dependent responses by chronic alterations of blood flow.

To determine whether the blood flow and O2 tension to which a blood vessel is chronically exposed could modulate endothelium-dependent responses, these parameters were altered in the dog either by causing partial occlusion of the femoral artery or by creating a fistula between the femoral artery and vein. Blood flow was reduced by 75% in the clamped artery; mean arterial pressure was unchanged. In the vessels proximal to the fistula, blood flow was elevated and O2 tensions were similar in the vein and artery. After 6 wk the femoral arteries and veins were excised, and their endothelium-dependent responses were studied in vitro. The endothelium-dependent relaxations to acetylcholine, adenosine diphosphate, and alpha 2-adrenergic stimulation were augmented in fistula-operated compared with sham-operated arteries. The responses to these agents in the clamp-operated vessels were not different from those of the sham-operated ones. Relaxation to arachidonic acid in the arteries showed an inverse relationship to blood flow. In the veins proximal to the fistula, the endothelium-dependent relaxations to acetylcholine were augmented and an endothelium-dependent relaxation to alpha 2-adrenergic stimulation was present; only a contractile response was observed in veins from the sham-operated limb in response to the latter. These studies suggest a pattern of increased endothelium-dependent relaxation in vessels exposed to chronically elevated blood flow.

Animals↗
PubMed1986

Effects of naftidrofuryl on adrenergic nerves, endothelium and smooth muscle in isolated canine blood vessels.

Experiments were designed to determine the effects of the vasoactive drug naftidrofuryl on vascular smooth muscle, endothelial cells and adrenergic nerves in isolated canine blood vessels. Naftidrofuryl inhibited contractions of basilar arteries (in a decreasing order of potency), evoked by 5-hydroxytryptamine greater than KCl = anoxia (in rings with endothelium) greater than prostaglandin F2 alpha = uridine-5'-triphosphate. Naftidrofuryl antagonized competitively the contractions evoked by 5-hydroxytryptamine in the femoral artery and the saphenous vein. Naftidrofuryl caused the release of an endothelium-derived relaxing factor(s) from the endothelium of femoral arteries. The compound depressed contractions of saphenous veins evoked by electrical stimulation of the adrenergic nerve endings, but not those caused by the indirect sympathomimetic amine tyramine or exogenous norepinephrine. In saphenous veins incubated previously with [3H]norepinephrine, the drug inhibited the contractions and the release of transmitter evoked by electrical stimulation. Thus, naftidrofuryl acts at different levels in the blood vessel wall to cause: release of endothelium-derived relaxing factor(s); inhibition of S2-serotonergic receptors on vascular smooth muscle; prejunctional inhibition of adrenergic neurotransmission; and nonselective inhibition of the contractile process in vascular smooth muscle, which is particularly pronounced in cerebral arteries.

Adrenergic Fibers↗
PubMed1986

Serotonin reduces coronary flow in the isolated heart of the spontaneously hypertensive rat.

Serotonin may cause vasodilatation or vasoconstriction. In hypertension the vasoconstrictor effects of serotonin predominate. Experiments were designed to study the effects of serotonin on coronary flow in isolated hearts of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The hearts were paced at constant rate and perfused by the Langendorff technique at constant pressure (75 cmH2O). In WKY rats serotonin (10-9 to 10-5 mol/l) caused concentration-dependent increases in coronary flow and a decrease in cardiac performance. In SHR, the monoamine caused concentration-dependent, partially reversible decreases in coronary flow, and a marked decrease in cardiac performance. The inhibitor of cyclo-oxygenase indomethacin prevented the decrease in coronary flow and cardiac performance caused by serotonin in SHR, but did not affect the increase in coronary flow in WKY rats. These experiments suggest that in the coronary circulation of SHR the response to serotonin is shifted from vasodilatation to vasoconstriction. The mediator of this vasoconstriction is probably a product of cyclo-oxygenase.

Animals↗
PubMed1985

Respiratory epithelium inhibits bronchial smooth muscle tone.

The aim of the present study was to determine whether or not the respiratory epithelium can modulate the responsiveness of bronchial smooth muscle. Paired rings of canine bronchi (4-6 mm OD), in some of which the epithelium had been removed mechanically (by rubbing the luminal surface), were mounted in physiological saline solution, gassed with 95% O2-5% CO2, and maintained at 37 degrees C. The presence or absence of the epithelium was confirmed by histological examination. Removal of the epithelium increased the contractile responses evoked by acetylcholine, histamine, and 5-hydroxytryptamine. Transmural nerve stimulation evoked similar peak responses in the presence and absence of epithelium. In unrubbed preparations, the peak response was followed by a gradual decrease when the stimulation was continued. This decrease, which persisted in the presence of propranolol, was not observed in epithelium-denuded preparations. In bronchial rings contracted with acetylcholine, isoproterenol produced concentration-dependent relaxations which were significantly greater in rings with epithelium compared with denuded rings. These results suggest that respiratory epithelial cells may generate an inhibitory signal to decrease the responsiveness of bronchial smooth muscle to contractile agonists and augment the effectiveness of inhibitory stimuli.

Acetylcholine↗
PubMed1984

Pharmacology of bucindolol in isolated canine vascular smooth muscle.

To determine the effects of bucindolol on isolated vascular smooth muscle, rings of canine coronary and femoral arteries and saphenous veins were suspended for isometric tension recording in organ chambers filled with physiological salt solution. Bucindolol (3 X 10(-10) to 1 X 10(-7) M) had a comparable inhibitory effect on relaxations induced by isoproterenol in coronary arteries (which contain postjunctional beta-1 adrenoceptors) and saphenous veins (which contain postjunctional beta-2 adrenoceptors). Bucindolol (1 X 10(-7) M) had no effect on relaxations induced by sodium nitroprusside during contractions evoked by prostaglandin F2 alpha in either saphenous veins or coronary arteries. Bucindolol also had weak (relative to its beta adrenoceptor effect) alpha adrenoceptor-antagonistic activity that was greater for postjunctional alpha-1 than alpha-2 adrenoceptors. In all tissues tested, bucindolol in concentrations greater than 1 X 10(-6) M caused relaxations of responses induced by various nonadrenergic agonists. Propranolol (5 X 10(-6) M) did not alter the direct inhibitory effect that bucindolol had on contractions of coronary arteries or saphenous veins evoked by prostaglandin F2 alpha; this inhibitory effect of bucindolol was independent of the endothelium. In superfused saphenous vein strips, previously incubated with [3H]norepinephrine, bucindolol (3 X 10(-7) to 1 X 10(-5) M) increased the basal efflux of [3H]norepinephrine and its [3H] metabolites. Bucindolol at 1 X 10(-7) M inhibited prejunctional beta adrenoceptors without affecting prejunctional alpha adrenoceptors. These experiments indicate that bucindolol in decreasing orders of activity 1) has nonselective beta adrenoceptor-antagonistic properties, 2) has a selective alpha-1 adrenoceptor-inhibitory effect and 3) has a nonspecific direct relaxing action on vascular smooth muscle.

Adrenergic beta-Antagonists↗
PubMed1983

Prejunctional beta-adrenoceptors in human and canine saphenous veins.

Experiments were designed to compare the functional importance of prejunctional beta-adrenoceptors in human and canine blood vessels. Rings of saphenous veins were mounted for isometric tension recording in organ chambers filled with physiological salt solution. Isoproterenol caused concentration-dependent relaxations of comparable magnitude during contractions of canine veins caused by electrical stimulation or norepinephrine. In the human veins, isoproterenol caused smaller relaxations during norepinephrine-induced contractions, and augmented the contractile response to electrical stimulation. Helical strips of veins were incubated with [3H]norepinephrine and mounted for superfusion and isometric tension recording. Isoproterenol augmented the release of intact labeled transmitter during electrical stimulation more in the human than in the canine vein. In veins from both species the effects of isoproterenol were inhibited by propranolol. These experiments demonstrate that the adrenergic nerves of the human saphenous vein have a greater responsiveness to prejunctional beta-adrenergic activation than those of the corresponding canine vessel. As a consequence, in the human vein, beta-adrenergic agonists augment, rather than depress the contractile response to activation of the adrenergic nerve endings.

Animals↗
PubMed1983

Contractions of canine vascular smooth muscle cells caused by ouabain are due to release of norepinephrine from adrenergic nerve endings.

Experiments were performed to determine whether the contractions of isolated canine blood vessels caused by ouabain are due solely to the release of endogenous norepinephrine. The response of segments of splenic arteries and veins and strips of splenic capsules to ouabain were compared before and after surgical sympathectomy. Successful denervation was demonstrated by absence of a contractile response to electrical stimulation, supersensitivity to exogenous norepinephrine, an extremely low content of endogenous norepinephrine, reduced accumulation of 3H-norepinephrine, and inability of electrical stimulation and tyramine to augment the overflow of 3H-norepinephrine. Ouabain augmented the overflow of 3H-norepinephrine from control but not from denervated splenic capsule. It caused contraction of control but not of denervated splenic arteries, veins, and capsules. Studies were also conducted in the same tissues and in segments of mesenteric and femoral arteries and of circular and longitudinal segments of the portal mesenteric vein before and after chemical sympathectomy with 6-hydroxydopamine. In these tissues, the contractile responses to electrical stimulation but not exogenous norepinephrine and prostaglandin F2 alpha were abolished. In the control tissues, ouabain caused strong contractions, whereas, in the denervated tissues, only a weak or no response to the glycoside occurred. The study demonstrates that, in isolated canine blood vessels, ouabain causes contraction of smooth muscle cells by virtue of its ability to release norepinephrine from the sympathetic nerves.

Adrenergic Fibers↗
PubMed1983

Alpha-1 adrenoceptors and calcium in isolated canine coronary arteries.

Experiments were designed to define the postjunctional alpha adrenoceptor subtype(s) in large canine coronary arteries and to determine the dependency of contractions due to their activation upon the entry of extracellular calcium. Rings of left circumflex coronary artery were mounted at their optimal length for isometric tension recording in organ chambers filled with physiological salt solution. Phenylephrine and cirazoline were full agonists relative to norepinephrine. Methoxamine was a partial agonist relative to norepinephrine whereas clonidine, xylazine, B-HT 920 and B-HT 933 produced minimal contractions. Prazosin competitively inhibited the contractile response to phenylephrine (pA2 = 8.6), whereas rauwolscine caused a noncompetitive inhibition and was more than 100 times less potent than prazosin at inhibiting the response to phenylephrine. Similar results were obtained using norepinephrine (in the presence of propranolol) as the agonist. The calcium-entry blockers nimodipine, verapamil and diltiazem inhibited contractions caused by norepinephrine, phenylephrine and cirazoline. Removal of extracellular calcium abolished the response to cirazoline. These results suggest that in large canine coronary arteries: 1) only alpha-1 adrenoceptors are present postjunctionally and 2) responses due to alpha-1 adrenoceptor activation are dependent upon extracellular calcium.

Adrenergic alpha-Agonists↗
PubMed1983

Effects of buflomedil on the responsiveness of canine vascular smooth muscle.

Experiments were designed to determine the effect of buflomedil on vascular responsiveness. Rings of canine arteries and veins were suspended for isometric tension recording at 37 degrees C. Buflomedil caused concentration-dependent inhibition of the contractile responses to norepinephrine, methoxamine, phenylephrine, clonidine, xylazine and sympathetic nerve activation, but not of the responses to potassium, prostaglandin F2 alpha, acetylcholine or 5-hydroxytryptamine. The inhibitory effect of buflomedil was not affected by endothelium removal but was reduced by chemical sympathectomy with 6-hydroxydopamine and by inhibitors of neuronal uptake. Strips of canine saphenous veins were superfused after incubation with [3H]norepinephrine. Buflomedil augmented the efflux of [3H]norepinephrine, 3,4-[3H]dihydroxyphenylglyol, 3,4-[3H]dihydroxymandelic acid and [3H]-3-methoxy-4-hydroxyphenylglycol under basal conditions and the overflow of [3H]norepinephrine, 3,4-[3H]dihydroxymandelic acid and 3,4-[3H] dihydroxyphenylglycol during sympathetic nerve activation. The augmentation by buflomedil of the release of [3H]norepinephrine evoked by electrical stimulation was prevented by phentolamine. In the perfused gracilis muscle of the anesthetized dog, buflomedil depressed the vasoconstrictor response to norepinephrine more than that evoked by angiotensin II. These experiments suggest that buflomedial blocks alpha adrenoceptors, but is not selective for either the alpha-1 or alpha-2 adrenoceptor subtype. The presence of adrenergic nerve endings appear to augment the postjunctional inhibitory effects of buflomedil.

Adrenergic alpha-Antagonists↗
PubMed1975

Similarity of blood flows using indocyanine prepared in saline or distilled water.

Directly measured blood flow pumped through a mixer circuit was compared to estimates of flow from indicator dilution curves derived from bolus injections of indocyanine green dye prepared in 0.9% saline (saline dye) and in triple-distilled water (3 D dye). At flows whose mean appearance time was 1.6 s, the mean error of estimate +/-SD of 2.3 +/- 5.1% using 3 D dye was significantly different (P less than 0.05) from that of 5.6 +/- 7.0% using saline dye. Essentially, there was no difference in estimates of blood flow with each dye solution when mean appearance time was increased to 3.8 s. Thus, the error, which was perhaps due to electrolyte in the concentrated indocyanine green dye (saline dye) and subsequent slowed rate of optical stabilization after dilution in plasma, is small and does not explain the overestimation by indocyanine dilution curves of blood flow in intact dogs.

Animals↗