Heme oxygenase substrates acutely lower blood pressure in hypertensive rats.
Heme oxygenase substrates acutely lower blood pressure in hypertensive rats.
复制标题
DOI：
10.1152/ajpheart.1996.271.3.h1132
复制
发表时间：
1996-09
期刊：
影响因子：
--
通讯作者：
Robert A. Johnson;M. Lavesa;Katie Deseyn;Matthew J. Scholer;A. Nasjletti
中科院分区：
文献类型：
--
作者：
Robert A. Johnson;M. Lavesa;Katie Deseyn;Matthew J. Scholer;A. Nasjletti
血红素加氧酶催化血红素代谢为胆绿素、游离铁和一氧化碳。本研究旨在确定用血红素加氧酶底物血红素-L-精氨酸或血红素-L-赖氨酸处理以刺激血红素加氧酶产物的形成是否可以降低大鼠的血压。血红素-L-精氨酸（45 μ mol/kg ip）和血红素-L-赖氨酸（45 μ mol/kg ip）使清醒的自发性高血压大鼠（SHR）的血压急剧下降约35 mmHg。对于这两种血红素加氧酶底物，这种作用被钝化的血红素加氧酶，锌次卟啉2，4-二甘醇的抑制剂预处理。血红素-L-赖氨酸盐也降低了脱氧皮质酮醋酸盐高血压大鼠和苯肾上腺素诱导的高血压大鼠的动脉压，表明血红素的血管抑制作用可以扩展到其他高血压模型。然而，无论是血红素-L-精氨酸或血红素-L-赖氨酸降低血压正常对照。血红素加氧酶产物胆绿素不能降低SHR的血压，血红素-L-赖氨酸盐的血管抑制作用不受去铁胺螯合游离铁预处理的影响。一氧化碳（12毫升/公斤ip）降低血压的SHR和大鼠高血压的苯肾上腺素输注，对血压没有影响的Wistar-Kyoto大鼠，并引起只有适度的血管抑制反应，血压正常的Sprague-Dawley大鼠。我们的结论是，血红素轴承制剂可以降低高血压大鼠的血压，推测通过血红素加氧酶介导的一氧化碳的形成。
Heme oxygenase catalyzes the metabolism of heme to biliverdine, free iron, and carbon monoxide. The current study was designed to determine if treatment with the heme oxygenase substrates heme-L-arginate or heme-L-lysinate, to stimulate formation of heme oxygenase products, can lower blood pressure in the rat. Heme-L-arginate (45 mumol/kg ip) and heme-L-lysinate (45 mumol/kg ip) acutely lowered blood pressure in awake spontaneously hypertensive rats (SHR) by approximately 35 mmHg. For both heme oxygenase substrates, this effect was blunted by pretreatment with an inhibitor of heme oxygenase, zinc deuteroporphyrin 2,4-bis glycol. Heme-L-lysinate also lowered arterial pressure in deoxycorticosterone acetate-salt hypertensive rats and in rats with phenylephrine-induced hypertension, indicating that the vasodepressive actions of heme may be extended to other hypertensive models. However, neither heme-L-arginate nor heme-L-lysinate decreased blood pressure in normotensive controls. The heme oxygenase product biliverdine did not lower blood pressure in SHR, and the vasodepressive actions of heme-L-lysinate were unaffected by pretreatment with deferoxamine to chelate free iron. Carbon monoxide (12 ml/kg ip) lowered blood pressure in SHR and in rats made hypertensive by phenylephrine infusion, had no effect on blood pressure in Wistar-Kyoto rats, and elicited only a modest vasodepressive response in normotensive Sprague-Dawley rats. We conclude that heme-bearing preparations can lower blood pressure in hypertensive rats, presumably via heme oxygenase-mediated formation of carbon monoxide.