利血平可诱导犬血管α2-肾上腺素能超敏反应和血小板α2-肾上腺素能受体上调。

Reserpine induces vascular alpha 2-adrenergic supersensitivity and platelet alpha 2-adrenoceptor up-regulation in dog.

作者信息

Estan L, Senard J M, Tran M A, Montastruc J L, Berlan M

机构信息

Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Faculté de Médecine, Toulouse, France.

出版信息

Br J Pharmacol. 1990 Oct;101(2):329-36. doi: 10.1111/j.1476-5381.1990.tb12710.x.

DOI:10.1111/j.1476-5381.1990.tb12710.x

PMID:2175232

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1917705/

Abstract

The aim of the present study was to investigate the influence of catecholamine levels on the regulation of alpha 2-adrenoceptor sensitivity in dogs. 2. Blood pressure and heart rate values at rest, plasma catecholamine levels, platelet and adipocyte alpha 2-adrenoceptors as well as the alpha 2-mediated cardiovascular responses to clonidine (10 micrograms kg-1 i.v., after alpha 1-, beta-adrenoceptor plus muscarinic blockade) or noradrenaline (0.5, 1, 2 and 4 micrograms kg-1 i.v. after alpha 1- and beta-adrenoceptor blockade) were measured before and after reserpine treatment (0.1 mg kg-1 day-1 s.c. over 15 days). 3. Reserpine induced a significant decrease in resting systolic and diastolic blood pressures (213 +/- 2/87 +/- 6 mmHg before vs 158 +/- 5/59 +/- 3 mmHg after treatment) as well as in heart rate (91 +/- 2 beats min-1 before vs 76 +/- 3 beats min-1 after treatment). 4. A 5 min tilt test performed under chloralose anesthesia, failed to modify blood pressure before treatment whereas it induced a significant fall in the same animals after the 15 day treatment. Plasma levels of noradrenaline significantly decreased (262 +/- 58 vs 66 +/- 31 pg ml-1) whereas plasma adrenaline levels were unchanged. 5. The alpha 2-mediated pressor responses to noradrenaline were significantly increased after reserpine. Clonidine induced a marked pressor effect (+72 and +45% in systolic and diastolic blood pressures respectively) after reserpine treatment. This effect was suppressed by administration of RX-821002, a new specific alpha 2-adrenoceptor antagonist. 6. Reserpine treatment significantly increased platelet alpha 2-adrenoceptor number (identified with [3H]- yohimbine or [3H]-RX821002) with no change in Kd values. alpha 2-Adrenoceptor number remained unchanged in adipocytes (identified with [3H]-RX821002). 7. These results show that a 15 day treatment with reserpine induces a vascular alpha 2-adrenergic supersensitivity and an up-regulation in platelet alpha 2-adrenoceptors. In contrast, this phenomenon does not involve all the tissues since adipocyte alpha 2-adrenoceptors escape the effect of reserpine. We suggest that the levels of plasma noradrenaline play an important role in the regulation of the platelet and vascular alpha 2-adrenoceptors. In contrast, adipocyte alpha 2-adrenoceptors are not affected by changes in plasma noradrenaline levels.

摘要

本研究的目的是探讨儿茶酚胺水平对犬α2 -肾上腺素能受体敏感性调节的影响。2. 在利血平治疗（0.1 mg kg-1 皮下注射，持续15天）前后，测量静息时的血压和心率值、血浆儿茶酚胺水平、血小板和脂肪细胞α2 -肾上腺素能受体，以及α2介导的对可乐定（10微克 kg-1 静脉注射，在α1 -、β -肾上腺素能受体加毒蕈碱阻断后）或去甲肾上腺素（0.5、1、2和4微克 kg-1 静脉注射，在α1 -和β -肾上腺素能受体阻断后）的心血管反应。3. 利血平导致静息收缩压和舒张压显著降低（治疗前为213±2/87±6 mmHg，治疗后为158±5/59±3 mmHg），心率也降低（治疗前为91±2次/分钟，治疗后为76±3次/分钟）。4. 在氯醛糖麻醉下进行的5分钟倾斜试验，治疗前未能改变血压，而在15天治疗后，同组动物血压显著下降。去甲肾上腺素的血浆水平显著降低（262±58对66±31 pg/ml），而肾上腺素的血浆水平未改变。5. 利血平后，α2介导的对去甲肾上腺素的升压反应显著增强。利血平治疗后，可乐定诱导出明显的升压作用（收缩压和舒张压分别升高72%和45%）。这种作用被新型特异性α2 -肾上腺素能受体拮抗剂RX - 821002的给药所抑制。6. 利血平治疗显著增加血小板α2 -肾上腺素能受体数量（用[3H]-育亨宾或[3H]-RX821002鉴定），Kd值无变化。脂肪细胞中的α2 -肾上腺素能受体数量（用[3H]-RX821002鉴定）保持不变。7. 这些结果表明，15天的利血平治疗诱导血管α2 -肾上腺素能超敏反应和血小板α2 -肾上腺素能受体上调。相比之下，这种现象并不涉及所有组织，因为脂肪细胞α2 -肾上腺素能受体不受利血平的影响。我们认为血浆去甲肾上腺素水平在血小板和血管α2 -肾上腺素能受体的调节中起重要作用。相比之下，脂肪细胞α2 -肾上腺素能受体不受血浆去甲肾上腺素水平变化的影响。