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Biomedical subjects

M Axelsson

Publications and source records attributed to M Axelsson.

At least 19 recordsLinked to original sources
PubMed2001

Nitric oxide, a potent vasodilator of the aortic anastomosis in the estuarine crocodile, Crocodylus porosus.

The effects of five neuropeptides (CGRP, SOM, SP, NPY, VIP), L-NAME (nitric oxide synthase inhibitor), and adrenaline on the contractile tone of the aortic anastomosis in the estuarine crocodile, Crocodylus porosus, were investigated. None of the neuropeptides, which had previously been found to be present in the aortic anastomosis, had any direct effect on the tension developed by ring preparations. L-NAME itself significantly increased the basal tone of the vascular ring preparations, suggesting a tonic release of nitric oxide in the preparation. Adrenaline produced concentration-dependent vasoconstrictions that were counteracted by profound reflex vasodilatations that were susceptible to blockade by L-NAME. Immunohistochemistry revealed the presence of nitric oxide synthase and tyrosine hydroxylase-containing (indicating the presence of a adrenergic innervation) nerve fibres in the adventitia and adventitio-medial border of the aortic anastomosis. These data demonstrate opposing actions of adrenaline and nitric oxide on the vascular smooth muscle in the anastomosis of the C. porosus. The morphology of the anastomosis, with the extremely thick muscular vessel wall, suggests a sphincter-like function for this vessel that could be controlled mainly by adrenergic and nitrergic mechanisms.

Alligators and Crocodiles↗
PubMed2001

The calibre of the foramen of Panizza in Crocodylus porosus is variable and under adrenergic control.

The foramen of Panizza is located within the outflow tract of the crocodilian heart, between the left and right aortas. It has been suggested that the foramen of Panizza has a variable calibre, which could explain the profound changes in the distribution of flows and pressure profiles recorded in the right and left aortas. We investigated this possibility using a modified in-situ perfused heart preparation in combination with isolated strip preparations from the outflow tract. In the perfused heart preparation, bolus injections of adrenaline increased the resistance in the foramen of Panizza, indicating a decrease in its diameter. Isolated strip preparations from the outflow tract showed a concentration-dependent increase in tension in response to adrenaline, while vasoactive intestinal polypeptide caused a relaxation in adrenaline pre-contracted strip preparations. We propose that an increase in the diameter of the foramen of Panizza may be important during pulmonary to systemic shunts to allow blood to flow from the left to right aorta (reverse foramen flow) in order to supply the carotid and coronary arteries. During non-shunting conditions, a constricted foramen may prevent excess flow from the right to left aorta during diastole.

Alligators and Crocodiles↗
PubMed2001

Large veins in the Atlantic cod (Gadus morhua) and the rainbow trout (Oncorhynchus mykiss) are innervated by neuropeptide-containing nerves.

Previous studies have shown that fish veins are reactive to several hormones known to exist in the fish circulation. Besides this humoral control, another possible means of active regulation of venous return is by autonomic nervous control of venous tone. This study therefore investigated the presence of a perivascular innervation of major veins in the Atlantic cod (Gadus morhua) and the rainbow trout (Oncorhynchus mykiss) using immunohistochemical methods. Histological staining was employed to investigate the smooth muscle distribution in the vessel walls. Vasoactive intestinal polypeptide-immunoreactive nerve fibers were found to be widespread in the venous system of G. morhua and O. mykiss, while pituitary adenylate cyclase-activating polypeptide-immunoreactive fibers were demonstrated in the duct of Cuvier of both species. Fibers containing neurokinin A and/or substance P were found in the duct of Cuvier and the posterior cardinal vein of both species and in the hepatic portal vein of O. mykiss. Calcitonin-gene related peptide-immunoreactive fibers were present in the duct of Cuvier of both species and in the hepatic portal vein of O. mykiss. Galanin-immunoreactive fibers were found in the duct of Cuvier in O. mykiss and in the hepatic portal vein of both species. Co-existence of neuropeptides in the perivascular nerve fibers was investigated by double labelling. Vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide-immunoreactive fibers were found in both species. Vasoactive intestinal polypeptide/galanin-immunoreactive fibers and vasoactive intestinal polypeptide/calcitoningene related peptide-immunoreactive fibers were found in G. morhua but not in O. mykiss. This study gives further evidence for an active venoregulation by autonomic nerves in teleost fish.

Animals↗
PubMed2001

Gut blood flow in fish during exercise and severe hypercapnia.

This paper reviews the effects of exercise and hypercapnia on blood flow to the splanchnic circulation. Brief struggling behaviours are known to decrease blood flow to the gut (GBF). Likewise, prolonged swimming in unfed fish has been shown to reduce GBF in proportion to the increased oxygen uptake. Therefore, the normal postprandial increase in GBF theoretically should be impaired whenever fish are active. However, indirect evidence suggests that GBF is spared to some degree when fed fish swim continuously but at a cost (10-15%) to their critical swimming speed. Severe respiratory acidosis can be created by the new intensive aquaculture settings that use oxygen injection into re-circulated water. The only study so far to examine the effects of severe hypercapnia on GBF and its regulation showed that routine GBF and alpha-adrenergic control of GBF remained normal in unfed white sturgeon (Acipenser transmontanus). However, severe hypercapnia produced a hyperactive state and increased sensitivity of GBF to struggling. As a result, routine GBF was maintained for a short period of time. Thus, environmental changes such as severe hypercapnia can indirectly impact GBF through altered struggling behaviour, but the implications of the overall reduction in GBF to food assimilation have yet to be established.

Animals↗
PubMed2001

Risk factors associated with hindlimb lameness and degenerative joint disease in the distal tarsus of Icelandic horses.

The aim of this study was to evaluate potential risk factors associated with hindlimb lameness and radiographic signs of degenerative joint disease (DJD) in the distal tarsus in Icelandic horses. The material consisted of riding horses (n = 420) age 6-12 years sired by 17 selected sires representing all major breeding lines, and of riding horses (n = 194) in the same age range sired by other sires. The examination protocol included the following: interview with owners/trainers, assessment of conformation, motion evaluation and radiographic examination. At the interview, data related to factors outside the horse (environmental variables) and data associated directly with the horse (intrinsic variables) were obtained. Data analysis was performed in 2 steps: screening using bivariate analysis, followed by testing with a multivariate logistic regression model. In the multivariate analysis, the factors of sire, age when broken to saddle and stud show participation were strongly associated with the prevalence of lameness. Height at the croup and ability to perform different gaits were also associated with the prevalence of lameness, but to a lesser degree. The risk factors of age, tarsal angle and birthplace were significantly associated with radiographic signs of DJD in the distal tarsus. Neither the variation in applied training intensity, the use of a professional or amateur trainer nor the temperament or front limb action of the individual horse was significantly associated with the prevalence of hindlimb lameness and/or radiographic signs of DJD in the distal tarsus in the Icelandic horse.

Age Factors↗
PubMed2000

The transmembrane domain and the proton channel in proton-pumping transhydrogenases.

Proton-pumping nicotinamide nucleotide transhydrogenases are composed of three main domains, the NAD(H)-binding and NADP(H)-binding hydrophilic domains I (dI) and III (dIII), respectively, and the hydrophobic domain II (dII) containing the assumed proton channel. dII in the Escherichia coli enzyme has recently been characterised with regard to topology and a packing model of the helix bundle in dII is proposed. Extensive mutagenesis of conserved charged residues of this domain showed that important residues are betaHis91 and betaAsn222. The pH dependence of betaH91D, as well as betaH91C (unpublished), when compared to that of wild type shows that reduction of 3-acetylpyridine-NAD(+) by NADPH, i.e., the reverse reaction, is optimal at a pH essentially coinciding with the pK(a) of the residue in the beta91 position. It is therefore concluded that the wild-type transhydrogenase is regulated by the degree of protonation of betaHis91. The mechanisms of the interactions between dI+dIII and dII are suggested to involve pronounced conformational changes in a 'hinge' region around betaR265.

Amino Acid Sequence↗
PubMed2000

Proton translocating nicotinamide nucleotide transhydrogenase from E. coli. Mechanism of action deduced from its structural and catalytic properties.

Transhydrogenase couples the stereospecific and reversible transfer of hydride equivalents from NADH to NADP(+) to the translocation of proton across the inner membrane in mitochondria and the cytoplasmic membrane in bacteria. Like all transhydrogenases, the Escherichia coli enzyme is composed of three domains. Domains I and III protrude from the membrane and contain the binding site for NAD(H) and NADP(H), respectively. Domain II spans the membrane and constitutes at least partly the proton translocating pathway. Three-dimensional models of the hydrophilic domains I and III deduced from crystallographic and NMR data and a new topology of domain II are presented. The new information obtained from the structures and the numerous mutation studies strengthen the proposition of a binding change mechanism, as a way to couple the reduction of NADP(+) by NADH to proton translocation and occurring mainly at the level of the NADP(H) binding site.

Amino Acid Sequence↗
PubMed2000

Gastrointestinal blood flow in the red Irish lord, Hemilepidotus hemilepidotus: long-term effects of feeding and adrenergic control.

Cardiac output, blood flow to the coeliac and mesenteric arteries, dorsal aortic blood pressure and heart rate were recorded simultaneously at rest and postprandial for 6 days in a teleost, the red Irish lord (Hemilepidotus hemilepidotus). We anticipated that gastrointestinal blood flow would increase postprandially, supported by an increase in cardiac output. However, we had no predictions for either the exact time-course of this response, or for the regional distribution of blood flow between to the two major arteries comprising the splanchnic circulation. In resting, unfed animals, blood flow to the coeliac artery and mesenteric artery was 4.1 +/- 0.6 ml min(-1) kg(-1) and 4.9 +/-1.3 ml min(-1) kg(-1), respectively (mean +/- SEM, n = 7), which together represented 34% of cardiac output. Feeding increased blood flow to the coeliac and mesenteric arteries in a time-dependent manner. The increase in coeliac artery blood flow preceded that in the mesenteric artery, a finding that is consistent with the coeliac artery supplying blood to the liver and stomach, while the mesenteric artery supplies blood to the stomach and intestine. Coeliac blood flow had increased by 84 +/- 18% after 1 day and had a peak increase of 112 +/- 40% at day 4 postprandial. Mesenteric blood flow was not significantly elevated at day 1, but had increased by 94 +/- 19% at day 4 postprandial. Cardiac output also increased progressively, increasing by a maximum of 90 +/- 30% at day 4. Because the increase in cardiac output was adequate to meet the postprandial increase in gut blood flow, the postprandial decreases in vascular resistance for the coeliac and mesenteric circulations mirrored the increases in blood flow. Intra-arterial injections of adrenaline and noradrenaline into resting fish more than doubled coeliac and mesenteric vascular resistances, and blood flow decreased proportionately. This adrenergic vasoconstriction was totally abolished by pretreatment with the alpha-adrenoceptor antagonist phentolamine, which in itself approximately halved coeliac and mesenteric vascular resistances. These observations indicate a significant alpha-adrenergic tone in the gastrointestinal circulation of the red Irish lord, the loss of which could not entirely account for the post-prandial increase in gastrointestinal blood flow. Other control mechanisms are suggested.

Adrenergic alpha-Agonists↗
PubMed2000

Interactions between the soluble domain I of nicotinamide nucleotide transhydrogenase from Rhodospirillum rubrum and transhydrogenase from Escherichia coli. Effects on catalytic and H+-pumping activities.

Nicotinamide nucleotide transhydrogenase from Escherichia coli is composed of two subunits, the alpha and the beta subunits, each of which contains a hydrophilic domain, domain I and III, respectively, as well as several transmembrane helices, collectively denoted domain II. The interactions between domain I from Rhodospirillum rubrum (rrI) and the intact or the protease-treated enzyme from E. coli was investigated using the separately expressed and purified domain I from R. rubrum, and His-tagged intact and trypsin-treated E. coli transhydrogenase. Despite harsh treatments with, e.g. detergents and denaturing agents, the alpha and beta subunits remained tightly associated. A monoclonal antibody directed towards the alpha subunit was strongly inhibitory, an effect that was relieved by added rrI. In addition, rrI also reactivated the trypsin-digested E. coli enzyme in which domain I had been partly removed. This suggests that the hydrophilic domains I and III are not in permanent contact but are mobile during catalysis while being anchored to domain II. Replacement of domain I of intact, as well as trypsin-digested, E. coli transhydrogenase with rrI resulted in a markedly different pH dependence of the cyclic reduction of 3-acetyl-pyridine-NAD+ by NADH in the presence of NADP(H), suggesting that the protonation of one or more protonable groups in domain I is controlling this reaction. The reverse reaction and proton pumping showed a less pronounced change in pH dependence, demonstrating the regulatory role of domain II in these reactions.

Amino Acid Sequence↗
PubMed2000

Cardiovascular actions of python bradykinin and substance P in the anesthetized python, Python regius.

The cardiovascular actions of python bradykinin (BK) and substance P (SP) have been investigated in the anesthetized ball python, Python regius. Bolus intra-arterial injections of python BK (0.03-3 nmol/kg) produced concentration-dependent increases in arterial blood pressure, heart rate (HR), and cardiac output concomitant with small decreases in systemic resistance and stroke volume. Intra-arterial injection of 3 nmol/kg python BK produced a tenfold increase in circulating concentration of norepinephrine, but epinephrine levels did not change. BK-induced tachycardia was attenuated (>90%) by the beta-adrenergic receptor antagonist sotalol, and the hypertensive response was attenuated (>70%) by the alpha-adrenergic receptor antagonist prazosin, indicating that effects of python BK are mediated at least in part by activation of the extensive network of adrenergic neurons present in vascular tissues. Bolus intra-arterial injections of python SP in the range 0. 01-30 pmol/kg produced concentration-dependent decreases in arterial blood pressure and systemic peripheral resistance concomitant with increases in cardiac output and stroke volume but with only minor effects on HR. The data suggest that kinins play a physiologically important role in cardiovascular regulation in the python.

Adrenergic alpha-Antagonists↗
PubMed2000

The emetic reflex in a reptile (Crocodylus porosus).

The emetic (vomiting) reflex in a crocodilian, Crocodylus porosus, was characterised for the first time using the plant alkaloid veratrine (5 mg kg(-)(1) i.v. or i.p.) as an emetic stimulus. The latency to the onset of vomiting was 8.0+/-0.9 min (mean +/- s.e.m., N=5 animals). Vomiting was preceded by a clearly defined set of prodromal behaviours including, in temporal sequence, rhythmic contraction of the pharynx, sneezing and jaw snapping. Expulsion of vomitus was not particularly forceful and was accompanied by lateral shaking of the head. Physiological studies revealed that vomiting was accompanied by oscillatory (9.1+/-0.7 oscillations over 29.7+/-3. 6 s, N=9 episodes in three animals) increases in intraperitoneal pressure (7.0+/-0.9 kPa, cf. 0.7+/-0.1 kPa during respiration). The significance of these results is discussed in the context of the role(s) of vomiting as a protective reflex and as a mechanism for removal of indigestible food residues (e.g. fur, claws) from the gut.

Abdomen↗
PubMed2000

Radiographic and clinical survey of degenerative joint disease in the distal tarsal joints in Icelandic horses.

The prevalence of degenerative joint disease (DJD) in the distal tarsal joints and the relation between radiographic and clinical signs compatible with the disease were estimated in a population of Icelandic horses used for riding. The material consisted of 614 horses age 6-12 years (mean age = 7.9 years). Radiographs with 3 projections of each tarsus were made and a clinical examination, including palpation of the medial aspect of the distal tarsus and motion evaluation of the hindlimbs before and after a flexion test of the tarsus, was performed. Radiographic signs of DJD in the distal tarsal joints were found in 30.3% of the horses and the prevalence was strongly correlated with age. Hindlimb lameness before and after flexion test and palpation abnormalities were significantly associated with the radiographic findings. The lameness was usually mild and, in most cases, detectable only after the flexion test. The prevalence of lameness was not significantly correlated with age. Lameness could not be predicted by details of the radiographic findings.

Age Factors↗
PubMed1999

Mapping of residues in the NADP(H)-binding site of proton-translocating nicotinamide nucleotide transhydrogenase from Escherichia coli. A study of structure and function.

Conformational changes in proton pumping transhydrogenases have been suggested to be dependent on binding of NADP(H) and the redox state of this substrate. Based on a detailed amino acid sequence analysis, it is argued that a classical betaalphabetaalphabeta dinucleotide binding fold is responsible for binding NADP(H). A model defining betaA, alphaB, betaB, betaD, and betaE of this domain is presented. To test this model, four single cysteine mutants (cfbetaA348C, cfbetaA390C, cfbetaK424C, and cfbetaR425C) were introduced into a functional cysteine-free transhydrogenase. Also, five cysteine mutants were constructed in the isolated domain III of Escherichia coli transhydrogenase (ecIIIH345C, ecIIIA348C, ecIIIR350C, ecIIID392C, and ecIIIK424C). In addition to kinetic characterizations, effects of sulfhydryl-specific labeling with N-ethylmaleimide, 2-(4'-maleimidylanilino)naphthalene-6-sulfonic acid, and diazotized 3-aminopyridine adenine dinucleotide (phosphate) were examined. The results are consistent with the view that, in agreement with the model, beta-Ala348, beta-Arg350, beta-Ala390, beta-Asp392, and beta-Lys424 are located in or close to the NADP(H) site. More specifically, beta-Ala348 succeeds betaB. The remarkable reactivity of betaR350C toward NNADP suggests that this residue is close to the nicotinamide moiety of NADP(H). beta-Ala390 and beta-Asp392 terminate or succeed betaD, and are thus, together with the region following betaA, creating the switch point crevice where NADP(H) binds. beta-Asp392 is particularly important for the substrate affinity, but it could also have a more complex role in the coupling mechanism for transhydrogenase.

Amino Acid Sequence↗
PubMed1999

Cardiovascular responses to adenosine in the antarctic fish pagothenia borchgrevinki

We have investigated the effects of adenosine on the cardiovascular system of the Antarctic fish Pagothenia borchgrevinki. Continuous measurements of ventral and dorsal aortic blood pressures, heart rate (fh) and ventral aortic blood flow (cardiac output, q_dot ) were made using standard cannulation techniques and a single-crystal Doppler flowmeter. On line measurements of arterial P(O2) were made using an oxygen electrode connected to an extracorporeal loop. Adenosine (10 nmol kg(-)(1)) and the specific A(1)-receptor agonist N(6)-cyclopentyladenosine (CPA) elicited biphasic changes in the branchial and systemic resistances. While there was an initial decrease in the branchial resistance followed by an increase, the opposite was true for the systemic response. The resistance changes were significantly attenuated by aminophylline (a P(1)-receptor antagonist) and 8-cyclopentyltheophylline (CPT; an A(1)-receptor antagonist). In addition, adenosine induced an aminophylline-sensitive decrease in the arterial P(O2). The reduction was attenuated when pre-injection arterial P(O2) was low. Adenosine and CPA also caused a marked reduction in fh, with CPA being more potent. The bradycardia was blocked by aminophylline and CPT, demonstrating an involvement of A(1) receptors in this response.

Journal Article↗
PubMed1998

Peptidergic control of gastrointestinal blood flow in the estuarine crocodile, Crocodylus porosus.

Peptidergic mechanisms influencing the resistance of the gastrointestinal vascular bed of the estuarine crocodile, Crocodylus porosus, were investigated. The gut was perfused in situ via the mesenteric and the celiac arteries, and the effects of different neuropeptides were tested using bolus injections. Effects on vascular resistance were recorded as changes in inflow pressures. Peptides found in sensory neurons [substance P, neurokinin A, and calcitonin gene-related peptide (CGRP)] all caused significant relaxation of the celiac vascular bed, as did vasoactive intestinal polypeptide (VIP), another well-known vasodilator. Except for VIP, the peptides also induced transitory gut contractions. Somatostatin and neuropeptide Y (NPY), which coexist in adrenergic neurons of the C. porosus, induced vasoconstriction in the celiac vascular bed without affecting the gut motility. Galanin caused vasoconstriction and occasionally activated the gut wall. To elucidate direct effects on individual vessels, the different peptides were tested on isolated ring preparations of the mesenteric and celiac arteries. Only CGRP and VIP relaxed the epinephrine-precontracted celiac artery, whereas the effects on the mesenteric artery were variable. Somatostatin and NPY did not affect the resting tonus of these vessels, but somatostatin potentiated the epinephrine-induced contraction of the celiac artery. Immunohistochemistry revealed the existence and localization of the above-mentioned peptides in nerve fibers innervating vessels of different sizes in the gut region. These data support the hypothesis of an important role for neuropeptides in the control of the vascular bed of the gastrointestinal tract in C. porosus.

Alligators and Crocodiles↗