المؤلفون: Katrina J. Carter, Jaqueline K. Limberg, Rebecca E. Johansson, John W Harrell, Joshua J. Sebranek, Garrett L. Peltonen, Benjamin J. Walker, Marlowe W. Eldridge, William G. Schrage, J. Mikhail Kellawan

المصدر: Am J Physiol Heart Circ Physiol

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Nitric Oxide Synthase Type III, Physiology, Vasodilation, Nitric oxide, chemistry.chemical_compound, Physiology (medical), Internal medicine, Receptors, Adrenergic, beta, medicine, Humans, Cyclooxygenase Inhibitors, Obesity, Muscle, Skeletal, Receptor, omega-N-Methylarginine, biology, Isoproterenol, Skeletal muscle, Adrenergic beta-Agonists, Nitric oxide synthase, Blood pressure, medicine.anatomical_structure, Endocrinology, chemistry, Prostaglandin-Endoperoxide Synthases, biology.protein, Blood Vessels, Female, Cyclooxygenase, medicine.symptom, Cardiology and Cardiovascular Medicine, Ketorolac, Vasoconstriction, Research Article

الوصف: Central adiposity is associated with greater sympathetic support of blood pressure. β-adrenergic receptors (β-AR) buffer sympathetically mediated vasoconstriction and β-AR-mediated vasodilation is attenuated in preclinical models of obesity. With this information, we hypothesized β-AR vasodilation would be lower in obese compared with normal weight adults. Because β-AR vasodilation in normal weight adults is limited by cyclooxygenase (COX) restraint of nitric oxide synthase (NOS), we further explored the contributions of COX and NOS to β-AR vasodilation in this cohort. Forearm blood flow (FBF, Doppler ultrasound) and mean arterial blood pressure (MAP, brachial arterial catheter) were measured and forearm vascular conductance (FVC) was calculated (FVC = FBF/MAP). The rise in FVC from baseline (ΔFVC) was quantified during graded brachial artery infusion of isoproterenol (Iso, 1–12 ng/100 g/min) in normal weight (n = 36) and adults with obesity (n = 22) (18–40 yr old). In a subset of participants, Iso-mediated vasodilation was examined before and during inhibition of NOS [N(G)-monomethyl-l-arginine (l-NMMA)], COX (ketorolac), and NOS + COX (l-NMMA + ketorolac). Iso-mediated increases in FVC did not differ between groups (P = 0.57). l-NMMA attenuated Iso-mediated ΔFVC in normal weight (P = 0.03) but not adults with obesity (P = 0.27). In normal weight adults, ketorolac increased Iso-mediated ΔFVC (P < 0.01) and this response was lost with concurrent l-NMMA (P = 0.67). In contrast, neither ketorolac (P = 0.81) nor ketorolac + l-NMMA (P = 0.40) altered Iso-mediated ΔFVC in adults with obesity. Despite shifts in COX and NOS, β-AR vasodilation is preserved in young adults with obesity. These data highlight the presence of a compensatory shift in microvascular control mechanisms in younger humans with obesity. NEW & NOTEWORTHY We examined β-adrenergic receptor-mediated vasodilation in skeletal muscle of humans with obesity and normal weight. Results show that despite shifts in the contribution of cyclooxygenase and nitric oxide synthase, β-adrenergic-mediated vasodilation is relatively preserved in young, otherwise healthy adults with obesity. These data highlight the presence of subclinical changes in microvascular control mechanisms early in the obesity process and suggest duration of obesity and/or the addition of primary aging may be necessary for overt dysfunction.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aa8e09b1715c554d28626853121bf47fTest
https://doi.org/10.1152/ajpheart.00449.2021Test

المؤلفون: Nabiha Yusuf, Mohammad Asif Sherwani, Vasundhara Kain, Jeevan Kumar Jadapalli, Griffin W. Wright, Ravi Sonkar, Ganesh V. Halade

المصدر: American Journal of Physiology-Heart and Circulatory Physiology. 315:H1091-H1100

مصطلحات موضوعية: Male, 0301 basic medicine, Cachexia, Time Factors, Contraction (grammar), Physiology, Lipoxygenase, Apoptosis, 030204 cardiovascular system & hematology, Ventricular Function, Left, 0302 clinical medicine, Cardiac toxicity, polycyclic compounds, Medicine, Antibiotics, Antineoplastic, Ventricular Remodeling, biology, Organ Size, Cytokines, Cardiology and Cardiovascular Medicine, Signal Transduction, Research Article, medicine.drug, Chronic exposure, Heart Diseases, Heart Ventricles, macromolecular substances, Gene Expression Regulation, Enzymologic, 03 medical and health sciences, Inflammation resolution, Physiology (medical), Animals, Doxorubicin, Splenic Diseases, Dose-Response Relationship, Drug, business.industry, Macrophages, Myocardium, organic chemicals, technology, industry, and agriculture, Germinal center, Fibrosis, Cardiotoxicity, Mice, Inbred C57BL, carbohydrates (lipids), 030104 developmental biology, Prostaglandin-Endoperoxide Synthases, Cancer research, biology.protein, Cyclooxygenase, business, Spleen

الوصف: Doxorubicin (DOX) is a widely used drug for cancer treatment as a chemotherapeutic agent. However, the cellular and integrative mechanism of DOX-induced immunometabolism is unclear. Two-month-old male C57BL/6J mice were divided into high- and low-dose DOX-treated groups with a maintained saline control group. The first group was injected with a high dose of DOX (H-DOX; 15 mg·kg−1·wk−1), and the second group was injected with 7.5 mg·kg−1·wk−1 as a latent low dose of DOX (LL-DOX). H-DOX treatment led to complete mortality in 2 wk and 70% survival in the LL-DOX group compared with the saline control group. Therefore, an additional group of mice was injected with an acute high dose of DOX (AH-DOX) and euthanized at 24 h to compare with LL-DOX and saline control groups. The LL-DOX and AH-DOX groups showed obvious apoptosis and dysfunctional and structural changes in cardiac tissue. Splenic contraction was evident in AH-DOX- and LL-DOX-treated mice, indicating the systems-wide impact of DOX on integrative organs of the spleen, which is essential for cardiac homeostasis and repair. DOX dysregulated splenic-enriched immune-sensitive lipoxygenase and cyclooxygenase in the spleen and left ventricle compared with the saline control group. As a result, lipoxygenase-dependent D- and E-series resolvin precursors, such as 16HDoHE, 4HDoHE, and 12-HEPE, as well as cyclooxygenase-mediated PG species (PGD2, PGE2, and 6-keto-PG2α) were decreased in the left ventricle, suggestive of defective immunometabolism. Both AH-DOX and LL-DOX induced splenic contraction and expansion of red pulp with decreased CD169+ metallophilic macrophages. AH-DOX intoxicated macrophages in the spleen by depleting CD169+ cells in the acute setting and sustained the splenic macrophage loss in the chronic phase in the LL-DOX group. Thus, DOX triggers a vicious cycle of splenocardiac cachexia to facilitate defective immunometabolism and irreversible macrophage toxicity and thereby impaired the inflammation-resolution program. NEW & NOTEWORTHY Doxorubicin (DOX) triggered splenic mass loss and decreased CD169 with germinal center contraction in acute and chronic exposure. Cardiac toxicity of DOX is marked with dysregulation of immunometabolism and thereby impaired resolution of inflammation. DOX suppressed physiological levels of cytokines and chemokines with signs of splenocardiac cachexia.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c9ec3861df965a0f5671cf707f6d769Test
https://doi.org/10.1152/ajpheart.00290.2018Test

المؤلفون: Brian L. Fish, Md. Abdul Hye Khan, Amit Sharma, Eric P. Cohen, John D. Imig, Neil S. Mandel

المصدر: American Journal of Physiology-Heart and Circulatory Physiology. 310:H1695-H1701

مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Endothelium, Physiology, Indomethacin, Blood Pressure, Vasodilation, urologic and male genital diseases, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, Physiology (medical), Internal medicine, Animals, Medicine, Cyclooxygenase Inhibitors, Endothelial dysfunction, biology, business.industry, Total body irradiation, medicine.disease, Acetylcholine, Rats, Nitric oxide synthase, Arterioles, NG-Nitroarginine Methyl Ester, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, chemistry, Prostaglandin-Endoperoxide Synthases, Call for Papers, biology.protein, Endothelium, Vascular, Azotemia, Nitric Oxide Synthase, Cardiology and Cardiovascular Medicine, business, Whole-Body Irradiation, medicine.drug

الوصف: Chronic kidney disease is a known complication of hematopoietic stem cell transplant (HSCT) and can be caused by irradiation at the time of the HSCT. In our rat model there is a 6- to 8-wk latent period after irradiation that leads to the development of proteinuria, azotemia, and hypertension. The current study tested the hypothesis that decreased endothelial-derived factors contribute to impaired afferent arteriolar function in rats exposed to total body irradiation (TBI). WAG/RijCmcr rats underwent 11 Gy TBI, and afferent arteriolar responses to acetylcholine were determined at 1, 3, and 6 wk. Blood pressure and blood urea nitrogen were not different between control and irradiated rats. Afferent arteriolar diameters were not altered in irradiated rats. Impaired endothelial-dependent responses to acetylcholine were evident at 3 and 6 wk following TBI. Nitric oxide synthase (NOS), cyclooxygenase (COX), and epoxygenase (EPOX) contribution to acetylcholine dilator responses were evaluated. NOS inhibition with NG-nitro-l-arginine methyl ester (l-NAME) reduced acetylcholine responses by 50% in controls and 90% in 3-wk TBI rats. COX inhibition with indomethacin did not significantly alter the acetylcholine response in the presence or absence of l-NAME. EPOX inhibition with N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide significantly decreased acetylcholine responses (35%) in controls but did not significantly alter acetylcholine responses (4%) in TBI rats. Biochemical analysis revealed decreased urinary EPOX metabolites but no change in COX, NOS, or reactive oxygen species at 3 wk TBI. Taken together, these results indicate that afferent arteriolar endothelial dysfunction involves a decrease in EPOX metabolites that precedes the development of proteinuria, azotemia, and hypertension in irradiated rats.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fb00c6867a1c6161b02c8966f94d03b7Test
https://doi.org/10.1152/ajpheart.00023.2016Test

المؤلفون: Joshua J. Sebranek, Jacqueline K. Limberg, Marlowe W. Eldridge, William G. Schrage, J. Mikhail Kellawan, Garrett L. Peltonen, Rebecca E. Johansson, John W. Harrell

المصدر: American Journal of Physiology-Heart and Circulatory Physiology. 310:H756-H764

مصطلحات موضوعية: Adult, Male, Agonist, medicine.medical_specialty, Mean arterial pressure, Physiology, medicine.drug_class, Prostaglandin, Vasodilation, 030204 cardiovascular system & hematology, Microcirculation, 03 medical and health sciences, chemistry.chemical_compound, Integrative Cardiovascular Physiology and Pathophysiology, Sex Factors, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, Infusions, Intra-Arterial, Cyclooxygenase Inhibitors, Enzyme Inhibitors, omega-N-Methylarginine, biology, business.industry, Isoproterenol, Ultrasonography, Doppler, Adrenergic beta-Agonists, Nitric oxide synthase, Forearm, Endocrinology, chemistry, Prostaglandin-Endoperoxide Synthases, biology.protein, Omega-N-Methylarginine, Female, Cyclooxygenase, Nitric Oxide Synthase, Cardiology and Cardiovascular Medicine, business, Ketorolac, 030217 neurology & neurosurgery

الوصف: We tested the hypothesis that women exhibit greater vasodilator responses to β-adrenoceptor stimulation compared with men. We further hypothesized women exhibit a greater contribution of nitric oxide synthase and cyclooxygenase to β-adrenergic-mediated vasodilation compared with men. Forearm blood flow (Doppler ultrasound) was measured in young men ( n = 29, 26 ± 1 yr) and women ( n = 33, 25 ± 1 yr) during intra-arterial infusion of isoproterenol (β-adrenergic agonist). In subset of subjects, isoproterenol responses were examined before and after local inhibition of nitric oxide synthase [ NG-monomethyl-l-arginine (l-NMMA); 6 male/10 female] and/or cyclooxygenase (ketorolac; 5 male/5 female). Vascular conductance (blood flow ÷ mean arterial pressure) was calculated to assess vasodilation. Vascular conductance increased with isoproterenol infusion ( P < 0.01), and this effect was not different between men and women ( P = 0.41). l-NMMA infusion had no effect on isoproterenol-mediated dilation in men ( P > 0.99) or women ( P = 0.21). In contrast, ketorolac infusion markedly increased isoproterenol-mediated responses in both men ( P < 0.01) and women ( P = 0.04) and this rise was lost with subsequent l-NMMA infusion (men, P < 0.01; women, P < 0.05). β-Adrenergic vasodilation is not different between men and women and sex differences in the independent contribution of nitric oxide synthase and cyclooxygenase to β-mediated vasodilation are not present. However, these data are the first to demonstrate β-adrenoceptor activation of cyclooxygenase suppresses nitric oxide synthase signaling in human forearm microcirculation and may have important implications for neurovascular control in both health and disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da8d0687b5d172d7a2ded9e2db372283Test
https://doi.org/10.1152/ajpheart.00886.2015Test

المؤلفون: Zhuoming Li, Ricky Y.K. Man, Yu Wang, Paul M. Vanhoutte

المصدر: American Journal of Physiology-Heart and Circulatory Physiology. 305:H1471-H1483

مصطلحات موضوعية: Male, Physiology, Vasodilator Agents, Blood Pressure, Pharmacology, Rats, Inbred WKY, Antioxidants, Ouabain, Potassium Channels, Calcium-Activated, chemistry.chemical_compound, Rats, Inbred SHR, Physiology (medical), Potassium Channel Blockers, medicine, Animals, Enzyme Inhibitors, Na+/K+-ATPase, Heme, Antihypertensive Agents, Dose-Response Relationship, Drug, biology, Bilirubin, Hyperpolarization (biology), Mesenteric Arteries, Rats, Up-Regulation, Vasodilation, Nitric oxide synthase, Heme oxygenase, Disease Models, Animal, chemistry, Biochemistry, Prostaglandin-Endoperoxide Synthases, Heme Oxygenase (Decyclizing), Hypertension, Apocynin, biology.protein, Hemin, Endothelium, Vascular, Nitric Oxide Synthase, Sodium-Potassium-Exchanging ATPase, Reactive Oxygen Species, Cardiology and Cardiovascular Medicine, medicine.drug

الوصف: Heme oxygenase (HO) converts heme to carbon monoxide, bilirubin, and free iron. The present study investigated whether or not HO-1 induction improves vascular relaxations attributable to endothelium-dependent hyperpolarization (EDH). Thirty-six-week-old spontaneously hypertensive rats were treated with the HO-1 inducer hemin, the HO inhibitor zinc protoporphyrin IX (II) (ZnPP), the antioxidant apocynin, or combinations of these compounds. Isolated mesenteric arteries were prepared for measurement of isometric tension, protein presence, and production of reactive oxygen species (ROS). Hemin potentiated acetylcholine-evoked EDH-type relaxations in the presence of Nω-nitro-l-arginine methyl ester (l-NAME) and indomethacin, while the combined treatment with ZnPP plus hemin prevented these improvements. The intermediate conductance Ca2+-activated K+ channel (IKCa) blocker TRAM-34 and the Na+-K+-ATPase blocker ouabain significantly impaired these hemin-potentiated relaxations. NS309-induced TRAM-34- and ouabain-sensitive relaxations were enhanced by hemin. K+-induced ouabain-sensitive relaxations and the expression of Na+-K+-ATPase were increased by hemin. Thus HO-1 induction improves EDH-type relaxations by augmented activation of IKCa and the downstream Na+-K+-ATPase. Treatment with apocynin showed a similar effect as hemin in impairing ROS production, enhancing K+-induced relaxations, and increasing Na+-K+-ATPase expression, without affecting the expression of HO-1. The effects of hemin and apocynin were not additive. These observations suggest that the effect of HO-1 induction on EDH-type relaxations is possibly due to its antioxidant properties. In vitro treatment with bilirubin, but not carbon monoxide, enhanced EDH-type relaxations and K+-induced ouabain-sensitive relaxations, suggesting that the production of bilirubin may be also involved. The present findings reveal that HO-1 may be a potential vascular-specific therapeutic strategy for endothelial dysfunction in hypertension.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2515a5d1858768b4a00a4e40e480228fTest
https://doi.org/10.1152/ajpheart.00962.2012Test

المؤلفون: Christopher T. Minson, Maggie Cooper Reinke, Naoto Fujii, Vienna E. Brunt

المصدر: American Journal of Physiology-Heart and Circulatory Physiology. 304:H667-H673

مصطلحات موضوعية: Male, medicine.medical_specialty, Mean arterial pressure, Microdialysis, Physiology, Vascular Biology and Microcirculation, Vasodilator Agents, Vasodilation, Nitric Oxide, Nitric oxide, Young Adult, chemistry.chemical_compound, Physiology (medical), Internal medicine, Laser-Doppler Flowmetry, medicine, Humans, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Skin, biology, business.industry, Microcirculation, Smoking, Area under the curve, equipment and supplies, Acetylcholine, Skin Aging, Ketorolac, NG-Nitroarginine Methyl Ester, Endocrinology, chemistry, Prostaglandin-Endoperoxide Synthases, Anesthesia, Prostaglandins, biology.protein, Female, Sodium nitroprusside, Cyclooxygenase, Cardiology and Cardiovascular Medicine, business, medicine.drug

الوصف: Cigarette smoking attenuates acetylcholine (ACh)-induced cutaneous vasodilation in humans, but the underlying mechanisms are unknown. We tested the hypothesis that smokers have impaired nitric oxide (NO)- and cyclooxygenase (COX)-dependent cutaneous vasodilation to ACh infusion. Twelve young smokers, who have smoked more than 5.2 ± 0.7 yr with an average daily consumption of 11.4 ± 1.2 cigarettes, and 12 nonsmokers were tested. Age, body mass index, and resting mean arterial pressure were similar between the groups. Cutaneous vascular conductance (CVC) was evaluated as laser-Doppler flux divided by mean arterial pressure, normalized to maximal CVC (local heating to 43.0°C plus sodium nitroprusside administration). We evaluated the increase in CVC from baseline to peak (CVCΔpeak) and area under the curve of CVC (CVCAUC) during a bolus infusion (1 min) of 137.5 μM ACh at four intradermal microdialysis sites: 1) Ringer (control), 2) 10 mM NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor), 3) 10 mM ketorolac (COX inhibitor), and 4) combination of l-NAME + ketorolac. CVCΔpeakand CVCAUCat the Ringer site in nonsmokers were greater than in smokers (CVCΔpeak, 42.9 ± 5.1 vs. 22.3 ± 3.5%max, P < 0.05; and CVCAUC, 8,085 ± 1,055 vs. 3,145 ± 539%max·s, P < 0.05). In nonsmokers, CVCΔpeakand CVCAUCat the l-NAME site were lower than the Ringer site (CVCΔpeak, 29.5 ± 6.2%max, P < 0.05; and CVCAUC, 5,377 ± 1,109%max·s, P < 0.05), but in smokers, there were no differences between the Ringer and l-NAME sites (CVCΔpeak, 16.8 ± 4.3%max, P = 0.11; and CVCAUC, 2,679 ± 785%max·s, P = 0.30). CVCΔpeakand CVCAUCwere reduced with ketorolac in nonsmokers (CVCΔpeak, 13.3 ± 3.6%max, P < 0.05; and CVCAUC, 1,967 ± 527%max·s, P < 0.05) and smokers (CVCΔpeak, 7.8 ± 1.8%max, P < 0.05; and CVCAUC, 1,246 ± 305%max·s, P < 0.05) and at the combination site in nonsmokers (CVCΔpeak, 15.9 ± 3.1%max, P < 0.05; and CVCAUC, 2,660 ± 512%max·s, P < 0.05) and smokers (CVCΔpeak, 11.5 ± 2.6%max, P < 0.05; and CVCAUC, 1,693 ± 409%max·s, P < 0.05), but the magnitudes were greater in nonsmokers ( P < 0.05). These results suggest that impaired ACh-induced skin vasodilation in young smokers is related to diminished NO- and COX-dependent vasodilation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eeb395ee41e66c9fc7f404a8a8a428b1Test
https://doi.org/10.1152/ajpheart.00731.2012Test

المؤلفون: Beth A. Parker, Paul D. Thompson, Donna M. Polk, Michael E. Tschakovsky, Amanda L. Augeri, Francis J. Kiernan

المصدر: American Journal of Physiology-Heart and Circulatory Physiology. 301:H1118-H1126

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Physiology, Vasodilator Agents, medicine.medical_treatment, Hyperemia, Vasodilation, Nitric Oxide, Nitroglycerin, Young Adult, Integrative Cardiovascular Physiology and Pathophysiology, Sex Factors, Physiology (medical), medicine.artery, Internal medicine, Laser-Doppler Flowmetry, medicine, Humans, Infusions, Intra-Arterial, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Brachial artery, Radial artery, Saline, Ultrasonography, Analysis of Variance, omega-N-Methylarginine, business.industry, Area under the curve, Ketorolac, Endocrinology, Prostaglandin-Endoperoxide Synthases, Regional Blood Flow, Dilator, Anesthesia, Radial Artery, Prostaglandins, cardiovascular system, Omega-N-Methylarginine, Female, Nitric Oxide Synthase, Cardiology and Cardiovascular Medicine, business, Blood Flow Velocity, circulatory and respiratory physiology, medicine.drug

الوصف: This study investigated the sex differences in the contribution of nitric oxide (NO) and prostaglandins (PGs) to flow-mediated dilation (FMD). Radial artery (RA) FMD, assessed as the dilatory response to 5-min distal cuff occlusion, was repeated after three separate brachial artery infusions of saline (SAL), NG-monomethyl-l-arginine (l-NMMA), and ketorolac (KETO) + l-NMMA in healthy younger men (M; n = 8) and women (W; n = 8). In eight subjects (4 M, 4W) RA FMD was reassessed on a separate day with drug order reversed (SAL, KETO, and l-NMMA + KETO). RA FMD was calculated as the peak dilatory response observed relative to baseline (%FMD) and expressed relative to the corresponding area under the curve shear stress (%FMD/AUC SS). l-NMMA reduced %FMD similarly and modestly ( P = 0.68 for sex * trial interaction) in M and W (all subjects: 10.0 ± 3.8 to 7.6 ± 4.7%; P = 0.03) with no further effect of KETO ( P = 0.68). However, all sex * trial and trial effects on %FMD/AUC SS for l-NMMA and KETO + l-NMMA were insignificant (all P > 0.20). There was also substantial heterogeneity of the magnitude and direction of dilator responses to blockade. After l-NMMA infusion, subjects exhibited both reduced ( n = 14; range: 11 to 78% decrease) and augmented ( n = 2; range: 1 to 96% increase) %FMD. Following KETO + l-NMMA, seven subjects exhibited reduced dilation (range: 10 to 115% decrease) and nine subjects exhibited augmented dilation (range: 1 to 212% increase). Reversing drug order did not change the nature of the findings. These findings suggest that RA FMD is not fully or uniformly NO dependent in either men or women, and that there is heterogeneity in the pathways underlying the conduit dilatory response to ischemia.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b5ef3d588237244209cb1e3abf020011Test
https://doi.org/10.1152/ajpheart.00400.2011Test

المؤلفون: John C. Longhurst, Liang-Wu Fu

المصدر: American Journal of Physiology-Heart and Circulatory Physiology. 298:H235-H244

مصطلحات موضوعية: Male, medicine.medical_specialty, Sympathetic nervous system, Physiology, Indomethacin, Myocardial Ischemia, Bradykinin, Neuropeptide, Thromboxane A2, chemistry.chemical_compound, Physiology (medical), Internal medicine, medicine, Animals, Vasoconstrictor Agents, Cyclooxygenase Inhibitors, Neurons, Afferent, business.industry, Drug Synergism, Heart, Articles, Spinal cord, Autonomic nervous system, medicine.anatomical_structure, Endocrinology, Spinal Cord, chemistry, Eicosanoid, Prostaglandin-Endoperoxide Synthases, 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, Circulatory system, Cats, Female, Cardiology and Cardiovascular Medicine, business

الوصف: Myocardial ischemia is a complex process leading to the simultaneous release of a number of mediators, including thromboxane A2(TxA2) and bradykinin (BK), that activate cardiac spinal afferents. The present study tested the hypothesis that TxA2and BK reciprocally interact to excite ischemically sensitive cardiac afferents. Nerve activity of single cardiac afferent units was recorded from the left sympathetic chain or rami communicantes (T2–T5) of anesthetized cats. Fifty-two ischemically sensitive afferents (conduction velocity = 0.27–3.35 m/s, 7 Aδ-fibers and 45 C-fibers) were identified. Repeated injections (1 μg) of BK into the left atrium (LA) 4 min after the administration of U-46619 (5 μg into the LA), a TxA2mimetic, induced a significantly larger cardiac afferent response than the first response to BK (0.61 ± 0.14 to 1.95 ± 0.29 vs. 0.66 ± 0.09 to 2.75 ± 0.34 impulses/s, first injection vs. second injection, n = 8). Conversely, blockade of TxA2receptors with BM-13,177 (30 mg/kg iv) attenuated the responses of eight other afferents to BK (1 μg into the LA) by 45%. In contrast, repeated BK (1 μg into the LA) induced consistent discharge activity in six separate afferents. We then observed that the coadministration of U-46619 (5 μg) and BK (1 μg into the LA) together caused a total response that was significantly higher than the predicted response by the simple addition of the individual responses. BK (1 μg) facilitated eight cardiac afferent responses to U-46619 (5 μg into the LA) by 64%. In contrast, repeated U-46619 (5 μg into the LA) without intervening BK stimulation evoked consistent responses in seven other ischemically sensitive afferents. Finally, inhibition of cyclooxygenase with indomethacin (5 mg/kg iv) eliminated the potentiating effects of BK on the cardiac afferent response to U-46619 (5 μg into the LA) but did not alter the afferent response to U-46619. These data suggest that BK and TxA2reciprocally interact to stimulate ischemically sensitive cardiac afferent endings leading to synergistic afferent responses and that the BK sensitization effect is mediated by cyclooxygenase products.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2c28fe96b08ebf1abafa7e61d09d872Test
https://doi.org/10.1152/ajpheart.00782.2009Test

المؤلفون: Yu-Jung Chen, John Quilley, Jing Li

المصدر: American Journal of Physiology-Heart and Circulatory Physiology. 294:H2305-H2312

مصطلحات موضوعية: Male, Physiology, medicine.medical_treatment, Indomethacin, Kidney, medicine.disease_cause, Antioxidants, chemistry.chemical_compound, Fenofibrate, Hydroxyeicosatetraenoic Acids, Insulin, Enzyme Inhibitors, Arachidonic Acid, biology, Perfusion, Nitric oxide synthase, NG-Nitroarginine Methyl Ester, medicine.anatomical_structure, Enzyme Induction, cardiovascular system, lipids (amino acids, peptides, and proteins), Arachidonic acid, Cytochrome P-450 CYP4A, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, Nitric Oxide, Diabetes Mellitus, Experimental, Nitric oxide, Cyclic N-Oxides, Aldehyde Reductase, Physiology (medical), Internal medicine, Diabetes mellitus, medicine, Animals, Hypoglycemic Agents, Cyclooxygenase Inhibitors, Benzothiazoles, Rats, Wistar, business.industry, Microcirculation, medicine.disease, Streptozotocin, Rats, Oxidative Stress, Endocrinology, chemistry, Prostaglandin-Endoperoxide Synthases, biology.protein, Phthalazines, Tyrosine, Spin Labels, Nitric Oxide Synthase, business, Oxidative stress

الوصف: We confirmed that release of 20-hydroxyeicosatetraenoic acid (20-HETE) from the isolated perfused kidney of diabetic rats is greatly reduced compared with age-matched control rats. The present studies were undertaken to examine potential mechanisms for the deficit in renal 20-HETE in rats with streptozotocin-induced diabetes of 3–4 wk duration. A role for oxidative stress was excluded, inasmuch as treatment of diabetic rats with tempol, an SOD mimetic, for 4 wk did not affect the renal release of 20-HETE. Similarly, chronic inhibition of nitric oxide formation with nitro-l-arginine methyl ester or aldose reductase with zopolrestat failed to alter the release of 20-HETE from the diabetic rat kidney. Inasmuch as 20-HETE may be metabolized by cyclooxygenase (COX), the expression/activity of which is increased in diabetes, we included indomethacin in the perfusate of the isolated kidney to inhibit COX but found no effect on 20-HETE release. Diabetic rats were treated for 3 wk with fenofibrate to increase expression of cytochrome P-450 (CYP4A) in an attempt to find an intervention that would restore release of 20-HETE from the diabetic rat kidney. However, fenofibrate reduced 20-HETE release in diabetic and control rat kidneys but increased expression of CYP4A. Only insulin treatment of diabetic rats for 2 wk to reverse the hyperglycemia and maintain blood glucose levels at

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bdb7afdaab53fb37b4b3d74c70e044d0Test
https://doi.org/10.1152/ajpheart.00868.2007Test

المؤلفون: Afsana Momen, Cynthia Hogeman, Jian Cui, Vernon Mascarenhas, Anandi Krishnan, Raman Moradkhan, Patrick M. McQuillan, Cheryl Blaha, Lawrence I. Sinoway

المصدر: American Journal of Physiology-Heart and Circulatory Physiology. 293:H1861-H1868

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Sympathetic nervous system, Sympathetic Nervous System, Physiology, Prostaglandin, Blood Pressure, Physical exercise, Article, chemistry.chemical_compound, Heart Rate, Physiology (medical), Internal medicine, Reflex, Humans, Medicine, Cyclooxygenase Inhibitors, Muscle, Skeletal, Evoked Potentials, Exercise, Hand Strength, biology, business.industry, body regions, Autonomic nervous system, Endocrinology, medicine.anatomical_structure, Eicosanoid, chemistry, Prostaglandin-Endoperoxide Synthases, Regional Blood Flow, Muscle Fatigue, Prostaglandins, biology.protein, Female, Cyclooxygenase, Animal studies, Cardiology and Cardiovascular Medicine, business, Ketorolac

الوصف: Animal studies suggest that prostaglandins in skeletal muscles stimulate afferents and contribute to the exercise pressor reflex. However, human data regarding a role for prostaglandins in this reflex are varied, in part because of systemic effects of pharmacological agents used to block prostaglandin synthesis. We hypothesized that local blockade of prostaglandin synthesis in exercising muscles could attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing exercise. Blood pressure (Finapres), heart rate, and MSNA (microneurography) were assessed in 12 young healthy subjects during static handgrip and postexercise muscle ischemia (PEMI) before and after local infusion of 6 mg of ketorolac tromethamine in saline via Bier block (regional intravenous anesthesia). In the second experiment (n = 10), the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased the prostaglandins synthesis to approximately 33% of the baseline. After ketorolac Bier block, the increases in MSNA from the baseline during the fatiguing handgrip was significantly lower than that before the Bier block (before ketorolac: Delta502 +/- 111; post ketorolac: Delta348 +/- 62%, P = 0.016). Moreover, the increase in total MSNA during PEMI after ketorolac was significantly lower than that before the Bier block (P = 0.014). Saline Bier block had no similar effect. The observations indicate that blockade of prostaglandin synthesis attenuates MSNA responses seen during fatiguing handgrip and suggest that prostaglandins contribute to the exercise pressor reflex.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::66b0d312e12d5732404afc98a24d44eaTest
https://doi.org/10.1152/ajpheart.00258.2007Test