Bradykinin and thromboxane A2reciprocally interact to synergistically stimulate cardiac spinal afferents during myocardial ischemia
| العنوان: | Bradykinin and thromboxane A2reciprocally interact to synergistically stimulate cardiac spinal afferents during myocardial ischemia |
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| المؤلفون: | John C. Longhurst, Liang-Wu Fu |
| المصدر: | American Journal of Physiology-Heart and Circulatory Physiology. 298:H235-H244 |
| بيانات النشر: | American Physiological Society, 2010. |
| سنة النشر: | 2010 |
| 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. |
| تدمد: | 1522-1539 0363-6135 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2c28fe96b08ebf1abafa7e61d09d872Test https://doi.org/10.1152/ajpheart.00782.2009Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d2c28fe96b08ebf1abafa7e61d09d872 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221539 03636135 |
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