PMID- 36348473 OWN - NLM STAT- MEDLINE DCOM- 20231006 LR - 20231006 IS - 2047-783X (Electronic) IS - 0949-2321 (Print) IS - 0949-2321 (Linking) VI - 27 IP - 1 DP - 2022 Nov 8 TI - Effects and related mechanism of alpha-adrenergic receptor inhibitor phentolamine in a rabbit model of acute pulmonary embolism combined with shock. PG - 238 LID - 10.1186/s40001-022-00842-5 [doi] LID - 238 AB - BACKGROUND: To observe the effect and mechanism of alpha-adrenergic receptor inhibitor phentolamine (PTL) in a rabbit model of acute pulmonary embolism (APE) combined with shock. METHODS: Twenty-four New Zealand rabbits were randomly divided into sham operation group (S group, n = 8), model group (M group, n = 8) and PTL group (n = 8), the model of APE combined with shock was established. Mean pulmonary arterial pressure (MPAP), peripheral mean arterial pressure (MAP) and pulmonary circulation time were evaluated. The expression levels of alpha(1) receptor, alpha(2) receptor and their downstream molecules in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions lung tissues were detected and compared, respectively. RESULTS: In M group, alpha receptor-related signaling pathways were significantly activated in both PE and non-PE areas as expressed by up-regulated alpha(1), alpha(2) receptor and phospholipase C (PLC); the expression level of phosphorylated protein kinase A (p-PKA) was significantly down-regulated; myosin light chain kinase (MLCK) and alpha-smooth muscle actin (alpha-SMA) levels were up-regulated. PTL treatment significantly improved pulmonary as well as systemic circulation failure: decreased MPAP, restored blood flow in non-PE area, shortened pulmonary circulation time, increased MAP, and restored the circulation failure. PTL induced significantly down-regulated expression of alpha(1) receptor and its downstream molecule PLC in both PE and non-PE area, the expression level of alpha(2) receptor was also down-regulated, the expression level of p-PKA was significantly up-regulated. PTL treatment can inhibit both alpha(1) and alpha(2) receptor-related signaling pathways in whole lung tissues, and inhibit Ca(2+) signaling pathways. The expression level of MLCK and alpha-SMA were significantly down-regulated. Compared with PE area, the changes of expression levels of alpha receptor and its downstream molecules were more significant in the non-PE region. CONCLUSION: In this model of APE combined with shock, the sympathetic nerve activity was enhanced in the whole lung, alpha(1) and alpha(2) receptor and their downstream signaling activation might mediate blood flow failure in the whole lung. PTL treatment can effectively restore pulmonary blood flow in non-PE area and improve pulmonary as well as systemic circulation failure possibly through down-regulating alpha(1) and alpha(2) receptor and their downstream signaling pathways. CI - (c) 2022. The Author(s). FAU - Wang, Yuting AU - Wang Y AD - Department of Cardiology, Wuhan Fourth Hospital, Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, HanZheng Street 473# QiaoKou District, Wuhan, 430033, China. FAU - Qiu, Li AU - Qiu L AD - Department of Cardiology, Wuhan Fourth Hospital, Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, HanZheng Street 473# QiaoKou District, Wuhan, 430033, China. FAU - Yu, Delong AU - Yu D AD - Department of Cardiology, Wuhan Fourth Hospital, Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, HanZheng Street 473# QiaoKou District, Wuhan, 430033, China. FAU - Yu, Yijun AU - Yu Y AD - Department of Cardiology, Wuhan Fourth Hospital, Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, HanZheng Street 473# QiaoKou District, Wuhan, 430033, China. FAU - Hu, Liqun AU - Hu L AD - Department of Cardiology, Wuhan Fourth Hospital, Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, HanZheng Street 473# QiaoKou District, Wuhan, 430033, China. FAU - Gu, Ye AU - Gu Y AD - Department of Cardiology, Wuhan Fourth Hospital, Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, HanZheng Street 473# QiaoKou District, Wuhan, 430033, China. yegu2003cn@163.com. LA - eng GR - 81900051/National Outstanding Youth Science Fund Project of National Natural Science Foundation of China/ PT - Journal Article DEP - 20221108 PL - England TA - Eur J Med Res JT - European journal of medical research JID - 9517857 RN - Z468598HBV (Phentolamine) RN - 0 (Receptors, Adrenergic, alpha) SB - IM MH - Animals MH - Rabbits MH - *Hominidae MH - Phentolamine/pharmacology MH - *Pulmonary Embolism/complications/drug therapy MH - Receptors, Adrenergic, alpha MH - *Shock PMC - PMC9641939 OTO - NOTNLM OT - Acute pulmonary embolism OT - Alpha receptors OT - Attenuation of pulmonary blood flow OT - Pulmonary vasoconstriction OT - Sympathetic activity COIS- The authors declare that they have no competing interests. EDAT- 2022/11/10 06:00 MHDA- 2022/11/11 06:00 PMCR- 2022/11/08 CRDT- 2022/11/09 00:06 PHST- 2022/08/17 00:00 [received] PHST- 2022/09/30 00:00 [accepted] PHST- 2022/11/09 00:06 [entrez] PHST- 2022/11/10 06:00 [pubmed] PHST- 2022/11/11 06:00 [medline] PHST- 2022/11/08 00:00 [pmc-release] AID - 10.1186/s40001-022-00842-5 [pii] AID - 842 [pii] AID - 10.1186/s40001-022-00842-5 [doi] PST - epublish SO - Eur J Med Res. 2022 Nov 8;27(1):238. doi: 10.1186/s40001-022-00842-5.