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A Ahluwalia

Publications and source records attributed to A Ahluwalia.

At least 37 records · Page 2Linked to original sources
PubMed2001

Endothelial cell adhesion on bioerodable polymers.

This paper presents the results of a preliminary screening of a new class of bioerodable polymers, partial esters of alternating copolymers of maleic anhydride and mono-methoxyoligoethyleneglycol vinyl ethers (PAM) for use in engineered vascular tissue. Different initial concentrations of PAM and human serum albumin (HSA) were spin-coated onto glass substrates and the surface properties of the resulting films and their relationship to endothelial cell adhesion was examined. An optimum PAM/HSA blend for use as the cell contact surface of a bioerodable scaffold was identified.

Journal Article↗
PubMed2001

Negative pressure rewarming vs. forced air warming in hypothermic postanesthetic volunteers.

We compared changes in core temperature and systemic heat balance with a new negative pressure/warming device (Vital Heat(R) ) that uses negative pressure combined with heat to facilitate warming in vasoconstricted postoperative patients to those resulting from passive insulation or forced air. Seven healthy volunteers were anesthetized and cooled to a tympanic membrane temperature near 34 degrees C. Anesthesia was discontinued and shivering was prevented by using meperidine. The vasoconstricted volunteers were rewarmed for 2 h using three randomly assigned methods: 1) Vital Heat plus cotton blanket; 2) one layer of cotton blanket; 3) forced-air warming. Thermal flux was recorded from 15 skin-surface sites; metabolic heat production was estimated from total body oxygen consumption. Metabolic heat production remained constant throughout the study. Systemic heat loss remained constant during warming with cotton blankets but decreased significantly during the other treatments. Systemic heat balance increased significantly more with forced air (140 +/- 21 kcal) than with Vital Heat (66 +/- 19 kcal) or cotton blankets (47 +/- 18 kcal). Core temperature increased no faster with Vital Heat warming (1.3 +/- 0.4 degrees C) than with a cotton blanket (1.2 +/- 0.4 degrees C). In contrast, core temperature increased more rapidly with forced air warming (2.6 +/- 0.6 degrees C). In this study we show that calories from a negative pressure rewarming device are largely constrained to the forearm and that heat does not flow to the core thermal compartment.

Adult↗
PubMed2001

Dial 1097 (toll free).

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed2001

An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthase-derived nitric oxide.

Myogenic tone is an important determinant of vascular tone and blood flow in small resistance arteries of certain vascular beds. The role of the endothelium in myogenic responses is unclear. We hypothesized that endothelium-derived NO release modulates myogenic constriction in small resistance arteries and that mesenteric small arteries from mice with targeted disruption of the gene for endothelial NO synthase (eNOS) (knockout mice) demonstrate greater myogenic tone than do wild-type mice. Third-order mesenteric arteries (approximately 200 micrometer) were isolated and mounted in a pressure myograph. Internal diameter was recorded over a pressure range of 10 to 80 mm Hg. Removal of the endothelium significantly (P<0.05) enhanced the magnitude of myogenic constriction in wild-type mice. Similarly, pretreatment of arteries with N(G)-nitro-L-arginine methyl ester (L-NAME; 300 micromol/L) produced a comparable significant (P<0.05) increase in myogenic tone, whereas indomethacin (5 micromol/L) had no effect. eNOS knockout arteries also exhibited myogenic constriction. Neither L-NAME nor indomethacin had any effect on myogenic tone in the arteries of eNOS knockout mice. However, blockade of potential endothelium-derived hyperpolarizing factor-like mechanisms via inhibition of K(+) flux using either apamin (100 nmol/L) with charybdotoxin (100 nmol/L), Ba(2+) (30 micromol/L) with ouabain (1 mmol/L), or 18alpha-glycyrrhetinic acid (100 micromol/L) significantly (P<0.01) enhanced myogenic constriction. This study demonstrates that basal endothelium-derived NO modulates myogenic tone in mesenteric small arteries of wild-type mice. However, eNOS knockout arteries display normal myogenic responsiveness despite the absence of basal NO activity. The data suggest that this compensatory effect is due to the activity of an endothelium-derived hyperpolarizing factor to normalize vascular tone.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Nepadutant Menarini Richerche.

Menarini Richerche is developing nepadutant, an NK2 antagonist, for the potential treatment of asthma and irritable bowel syndrome. The compound is in phase IIa trials in Belgium and Sweden for both these indications [359518].

Animals↗
PubMed2000

Association between kinin B(1) receptor expression and leukocyte trafficking across mouse mesenteric postcapillary venules.

Using intravital microscopy, we examined the role played by B(1) receptors in leukocyte trafficking across mouse mesenteric postcapillary venules in vivo. B(1) receptor blockade attenuated interleukin (IL)-1beta-induced (5 ng intraperitoneally, 2 h) leukocyte-endothelial cell interactions and leukocyte emigration ( approximately 50% reduction). The B(1) receptor agonist des-Arg(9)bradykinin (DABK), although inactive in saline- or IL-8-treated mice, caused marked neutrophil rolling, adhesion, and emigration 24 h after challenge with IL-1beta (when the cellular response to IL-1beta had subsided). Reverse transcriptase polymerase chain reaction and Western blot revealed a temporal association between the DABK-induced response and upregulation of mesenteric B(1) receptor mRNA and de novo protein expression after IL-1beta treatment. DABK-induced leukocyte trafficking was antagonized by the B(1) receptor antagonist des-arg(10)HOE 140 but not by the B(2) receptor antagonist HOE 140. Similarly, DABK effects were maintained in B(2) receptor knockout mice. The DABK-induced responses involved the release of neuropeptides from C fibers, as capsaicin treatment inhibited the responses. Treatment with the neurokinin (NK)(1) and NK(3) receptor antagonists attenuated the responses, whereas NK(2), calcitonin gene-related peptide, or platelet-activating factor receptor antagonists had no effect. Substance P caused leukocyte recruitment that, similar to DABK, was inhibited by NK(1) and NK(3) receptor blockade. Mast cell depletion using compound 48/80 reduced DABK-induced leukocyte trafficking, and DABK treatment was shown histologically to induce mast cell degranulation. DABK-induced trafficking was inhibited by histamine H(1) receptor blockade. Our findings provide clear evidence that B(1) receptors play an important role in the mediation of leukocyte-endothelial cell interactions in postcapillary venules, leading to leukocyte recruitment during an inflammatory response. This involves activation of C fibers and mast cells, release of substance P and histamine, and stimulation of NK(1), NK(3), and H(1) receptors.

Animals↗
PubMed2000

Endogenous factors involved in regulation of tone of arterial vasa vasorum: implications for conduit vessel physiology.

The walls of conduit blood vessels are nourished by diffusion of oxygen from luminal blood and from the vasa vasorum. The vasa vasorum, or 'vessels of a vessel', form a network of microvessels that lie in the adventitia and penetrate the outer media of the host vessel wall. Although the importance of the vasa vasorum in providing nutritional support is not well defined, obstruction of blood flow through these vessels has been implicated in the pathogenesis of certain cardiovascular diseases including atherosclerosis. This review focuses on the mechanisms that regulate tone in the vasa vasorum of large arteries and the functional implications of changes in reactivity of vasa vasorum.

Animals↗
PubMed2000

Kinin B(1) receptors and the cardiovascular system: regulation of expression and function.

Kinins are important peptide mediators of a diverse range of physiological and pathological functions of the cardiovascular system. The kinin peptides exert their effects by selective activation of two distinct G-protein coupled receptors termed B(1) and B(2). The principal kinin peptides involved in the acute regulation of cardiovascular function during normal physiology are bradykinin (BK) and Lys-BK which produce their effects via activation of B(2) receptors. The B(1) receptor is activated by the des-Arg(9)kinin metabolites namely des-Arg(9)BK and Lys-des-Arg(9)BK, the synthesis of which are increased during inflammation. The B(1) receptor, which is not constitutively expressed, is induced in various pathologies relating to inflammation. Recent investigations into the molecular mechanisms of B(1) receptor induction and their distribution and function in the cardiovascular system have shown that following an inflammatory stimulus the B(1) receptor is induced and may play an important role in modulation of cardiovascular function. This review summarises recent studies on B(1) receptor expression and function in the cardiovascular system and discusses the role of these receptors in regulation of circulatory homeostasis and their potential as therapeutic targets.

Animals↗
PubMed2000

Impaired vascular sensitivity to nitric oxide in the coronary microvasculature after endotoxaemia.

1. The effects of endotoxaemia on coronary vasodilator responses to bradykinin (BK), sodium nitroprusside (SNP) and nicardipine were investigated in the rat isolated heart perfused at constant flow ex vivo. 2. Dose-dependent reductions in coronary perfusion pressure reaching a maximum of 56+/-3 and 57+/-5 mmHg were observed for BK and SNP respectively. The BK response was biphasic, consisting of a rapid dilator response that was insensitive to N(G)nitro-L-arginine methyl ester (L-NAME, 0.1 mM) and a second slower component whose duration was attenuated by L-NAME. 3. Hearts obtained from rats treated with endotoxin (2.5 mg kg(-1), i.p.) for 2 or 6 h had increased basal coronary perfusion pressure and reduced vasodilator responses to BK or SNP. Dilator responses to nicardipine were not affected by endotoxin treatment. In vitro perfusion of hearts from endotoxin-treated rats with L-NAME (0.1 mM) restored SNP responses to control values. 4. Treatment with dexamethasone (1 mg kg(-1)), 1 h before endotoxin did not alter the endotoxin-induced impairment of dilator responses to BK or SNP. 5. These results show that coronary microvascular responses are altered following endotoxin exposure. Endotoxin results in increased coronary microvascular tone despite induction of NO synthase and inhibits the dilator response to BK and SNP, vasodilators that act via the release of NO. Responses to SNP in endotoxin-treated hearts were restored to control values in the presence of L-NAME suggesting that enhanced endogenous NO synthesis might saturate guanylate cyclase resulting in reduced response to NO donors. The reduced response to vasodilators and increased coronary resistance might be important in determining the response of the coronary circulation to systemic inflammation and infection.

Animals↗
PubMed2000

Effect of estradiol on estrogen receptor expression in rat uterine cell types.

In rodent uterus, both up- and down-regulation of estrogen receptor alpha (ERalpha) messenger ribonucleic acid (mRNA) and protein levels by estradiol has been demonstrated; however, it is not known which of the uterine compartments (endometrial epithelium, stroma, myometrium) respond to estradiol with autoregulation of ERalpha. The purpose of the present study was to investigate and compare the kinetics and cell type-specific effects of estradiol on uterine ERalpha expression in immature and adult rats. Ovariectomized female rats were injected s.c. with sesame oil or estradiol-17beta. Uteri were collected and analyzed for changes in ERalpha mRNA using RNase protection assays (RPA) and in situ hybridization using radiolabeled probes specific for ERalpha. Immunohistochemical analysis was performed with a polyclonal antibody specific to ERalpha. Expression of ERalpha in the uterine epithelial cells decreased at 3 and 6 h after estradiol administration to immature and adult rats, respectively. At 24 h, ERalpha mRNA levels in the immature and mature rat uterus were higher than pretreatment levels but returned to baseline by 72 h. Pretreatment with cycloheximide did not block the 3-h repressive effect of estradiol, suggesting that the estradiol-induced decrease in ERalpha mRNA occurs independent of new protein synthesis. A decrease in ERalpha mRNA and protein was also observed in uterine epithelia at 3 and 6 h after an estradiol injection to immature and adult rats, and intensity of both the in situ hybridization signal and the immunostaining in the epithelium increased at 24 and 72 h. However, the periluminal stromal cells in the adult uterus and the majority of stromal cells of the immature uterus appeared to have increased ERalpha expression. The results indicate that down-regulation of ERalpha in the epithelia and up-regulation of stromal ERalpha play a role in early events associated with estradiol-induced cell proliferation of the uterine epithelia.

Animals↗
PubMed2000

Expression of estrogen receptor coactivators in the rat uterus.

Nuclear receptor coactivators associate in a ligand-dependent manner with estrogen receptors (ER) and other nuclear receptors, and they enhance ligand-dependent transcriptional activation. This study examined basal coactivator expression in rat uterus to investigate if expression of these genes is regulated by estradiol-17 beta or tamoxifen. Ovariectomized mature and immature rats were injected with estradiol-17 beta, tamoxifen, or vehicle (i.e., sesame oil) alone. Uteri were collected and analyzed for changes in coactivator mRNA expression using Northern blot and in situ hybridization analyses. Constitutive uterine mRNA expression of switch protein for antagonist (SPA), SRC-1, GRIP1, RAC3, RIP140, and p300 mRNAs was observed in control uteri, and treatment with ER ligands did not alter coactivator mRNA levels. The data suggest that expression of these coactivator genes is not sensitive to estradiol or tamoxifen in the rat uterus. No cell type-specific pattern of expression was apparent in uterine sections from mature and immature rats; however, silver grains were more abundant in luminal and glandular epithelial cells compared with the stroma and myometrium, indicating that coactivator mRNA levels vary among the uterine compartments. Thus, to our knowledge, we show for the first time that there is constitutive expression of several uterine nuclear receptor coactivators in a physiological setting that remains insensitive to estrogenic regulation. Furthermore, we speculate that higher constitutive levels of coactivator expression in glandular and luminal epithelial cells may be associated with increased hormonal responsiveness by these uterine compartments.

Adaptor Proteins, Signal Transducing↗
PubMed2000

The microcirculation and inflammation: site of action for glucocorticoids.

The glucocorticoid hormones and their synthetic derivatives are potent suppressors of inflammatory and allergic pathologies. Their widespread efficacy is the result of multiple modes of action occurring predominantly at the level of the microcirculation. Indeed the glucocorticoids interfere with the function of all of the cellular components of the microcirculation associated with an inflammatory response. These agents inhibit vasodilatation of the arteriolar and capillary beds. therefore preventing the increase in blood flow that characterizes the initial stages of the inflammatory response. They also prevent increases in vascular permeability in the capillary and post-capillary venule, thereby reducing exudate formation. Finally, the glucocorticoids potently suppress leukocyte emigration across post-capillary venules. However, this promiscuity of the glucocorticoids to act at multiple sites also endows this class of (drugs with major side effects associated with chronic treatment. We propose that one way to progress forward is to understand better the effects of glucocorticoids within the microcirculation. This may aid identification of specific molecular sites of action and therefore the development of novel glucocorticoid molecules with fewer side effects.

Animals↗
PubMed1999

On the regulation of tone in vasa vasorum.

OBJECTIVE: The vasa vasorum form a network of microvessels in and around the walls of large blood vessels and are thought to be necessary to delivery oxygenated blood to the outer parts of the vessel wall that are inadequately nourished by diffusion from luminal blood. This study was undertaken to investigate directly the mechanisms which control tone in the vasa vasorum. METHODS: Arterial vasa vasorum were dissected from the walls of porcine or bovine thoracic aorta and mounted in a tension myograph. Concentration-response curves were constructed to vasoconstrictors; endothelin-1(ET-1), noradrenaline (NA) angiotensin II (Ang II) and thromboxane A2-mimetics (U44069 or U46619) or vasodilators; substance P (SP) bradykinin (BK), calcitonin gene-related peptide (CGRP) or isoprenaline. Strips of porcine aorta were mounted in 25 ml organ baths. RESULTS: Potent concentration-dependent contraction of vasa vasorum was produced by ET-1. NA was a weak constrictor, Ang II had no effect or produced contraction that underwent tachyphylaxis and thromboxane A2-mimetics had no effect. In contrast NA, Ang II, U-44069 and ET-1 all produced potent concentration-dependent contraction of aortic strips. SP and BK produced endothelium-dependent relaxation while CGRP produced endothelium-independent relaxation of ET-1-precontracted vasa vasorum. Isoprenaline had no relaxant effect. CONCLUSIONS: We have demonstrated functional responses of arterial vasa vasorum to vasodilators and vasoconstrictors. Additionally these microvessels appear to respond to constrictors differently from the large host vessel.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

B1 receptors as a new inflammatory target. Could this B the 1?

The kinins, particularly bradykinin (BK), are important mediators involved in both the initiation and progression of an inflammatory response. The pro-inflammatory effects of kinins are mediated by at least two receptors: the B2 subtype is expressed constitutively and the B1 receptor is induced following tissue inflammation and damage. The endogenous ligand for the B1 receptor is des-arg9BK, a cleavage product of the activity of carboxypeptidase on BK. Activation of B1 receptors produces a range of pro-inflammatory effects including oedema, pain and promotion of blood-borne leukocyte trafficking. In this article Amrita Ahluwalia and Mauro Perretti briefly describe the biology of BK and its receptors, and discuss the possible development of B1 receptor antagonists as novel anti-inflammatory agents.

Animals↗
PubMed1999

Inducible expression of the kinin B1 receptor in the endotoxemic heart: mechanisms of des-Arg9bradykinin-induced coronary vasodilation.

1 We have investigated the role of kinin B1 receptor induction in the endotoxemic rat heart and elucidated the mechanisms underlying B1 receptor-mediated coronary vasodilation. We also investigated the role of these receptors in endotoxin-induced hypotension. 2 Endotoxin treatment induced cardiac B1 receptor mRNA expression and promoted a coronary vasodilation response to des-Arg9bradykinin (DABK; ED50 = 149.4 pmol, n = 9) ex vivo peaking at 6 h. The B1 receptor antagonist des-Arg9-[Leu8]-BK (DALBK, 30 nM) significantly (P<0.05) inhibited the DABK-induced response (pA2 = 8.4, n = 5) whilst HOE140 (B2 receptor antagonist, 10 nM) was inactive (n = 4). 3 Removal of the endothelium or infusion with indomethacin (5 microM), but not L-NAME (300 microM) or ODQ (1 microM), inhibited (>85%, P<0.05, n = 5) the DABK-induced response. DABK caused a dose-dependent release of the prostacyclin metabolite, 6-keto-PGF1a (Emax = 0.3 ng ml-1, n = 6). 4 In vitro perfusion of hearts with endotoxin (1 microg ml-1, n = 6) or interleukin-1beta (5 ng ml-1, n = 6) induced B1 receptor mRNA expression and promoted a time-dependent vasodilation response to DABK. 5 Endotoxin treatment (6 h) in vivo promoted a hypotensive response to DABK (ED50 = 29.7 nmol kg-1, n = 10) which was antagonised by DALBK (3-6 nmol kg-1 min-1, P<0.05, n = 7). DALBK (3 nmol kg-1 min-1) and des-Arg10HOE140 (B1 receptor antagonist, 30 nmol kg-1 min-1) produced a 5.3% (n = 6, P<0.05) and 8.8% (n = 5, P<0.05) reversal, respectively, of endotoxin-induced hypotension. 6 In summary, we have shown that in endotoxemia activation of B1 receptors causes coronary vasodilation via endothelial prostacyclin release. Additionally, B1 receptor antagonists partially reversed endotoxin-induced hypotension. Therefore activation of B1 receptors may have a role to play in the vascular changes associated with endotoxemia.

Animals↗
PubMed1999

Endothelin alters the reactivity of vasa vasorum: mechanisms and implications for conduit vessel physiology and pathophysiology.

1 The walls of certain large blood vessels are nourished by the vasa vasorum, a network of microvessels that penetrate the adventitia and media of the vessel wall. The purpose of this study was to characterize endothelin-1 (ET-1)-mediated contraction of vasa and to investigate whether threshold concentrations of ET-1 alters the sensitivity to constrictors. Arterial vasa were dissected from the walls of porcine thoracic aorta and mounted in a tension myograph. 2 ET-1 and ETB-selective agonist, sarafotoxin 6c (S6c), produced concentration-dependent contraction. ETA receptor antagonist, BQ123 (10 microM), caused a biphasic rightward shift of ET-1 response curves. ETB receptor antagonist, BQ788 (1 microM), produced a rightward shift of response curves to ET-1 and S6c of 5- and 80 fold respectively. 3 ET-1 responses were abolished in Ca2+-free PSS but unaffected by selective depletion of intracellular Ca2+ stores. Nifedipine (10 microM), an L-type Ca2+ channel blocker, attenuated ET-1 responses by 44%. Inhibition of receptor-operated Ca2+ channels or non-selective cation entry using SKF 96365 (30 microM) and Ni2+ (1 mM) respectively, attenuated ET-1 contractions by 60%. 4 ET-1 (1-3 nM) enhanced responses to noradrenaline (NA) (4 fold) but not to thromboxane A2-mimetic, whilst K+ (10-20 mM) sensitized vasa to both types of constrictor. 5 Therefore, ET-1-induced contraction of isolated vasa is mediated by ETA and ETB receptors and involves Ca2+ influx through L-type and non-L-type Ca2+ channels. Furthermore elevation of basal tone of vasa vasorum alters the profile of contractile reactivity. These results suggest that ET-1 may be an important regulator of vasa vasorum reactivity.

Animals↗
PubMed1999

Langmuir-Blodgett films of antibodies as mediators of endothelial cell adhesion on polyurethanes.

The effect of endothelial cell adhesion on polyurethanes coated with Langmuir-Blodgett antibody films has been examined. The films were cross-linked with glutaraldehyde with the aim of providing a densely packed and covalently linked two-dimensional antibody network on the polyurethane surfaces. Our results demonstrate that although neither of the two polyurethanes examined were entirely suited to cellular adhesion, Langmuir-Blodgett antibody films, cross-linked with small concentrations of glutaraldehyde, are more suitable for endothelial cell adhesion than surfaces free of antibody.

Antibodies, Monoclonal↗