Recombinant adeno-associated virus-mediated human kallikrein gene therapy prevents high-salt diet-induced hypertension without effect on basal blood pressure  

作　　者：Jiang-tao YAN Tao WANG Juan LI Xiao XIAO Dao-wen WANG 

机构地区：[1]Department of Internal Medicine and Gene Therapy Center, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China [2]Molecular Pharmaceutics, The University of North Carolina School of Pharmacy, Chapel Hill, North Carolina, USA

出　　处：《Acta Pharmacologica Sinica》2008年第7期808-814,共7页中国药理学报（英文版）

基　　金：This study was supported by grants from National Natural Science Foundation Committee （No 30571841）, National 863 project （No 2006AA02A406）, 973 project （No 2007CB 512004）.

摘　　要：Aim： To investigate the effects of the expression of human kallikrein （HK） on basal level blood pressure and high-salt diet-induced hypertension. Methods： We delivered the recombinant adeno-associated viral （rAAV）-mediated HK （rAAV- HK） gene and rAAV-LacZ （as the control） to normal, adult Sprague-Dawley rats. The animals were administered a normal diet in the first 4 weeks, followed by a high-salt diet. The expression of HK in the rats was assessed by ELISA and RTPCR. Blood pressure and Na^＋ and K^＋ urinary excretion were monitored. Results： Under the normal diet, no obvious changes in blood pressure and Na^＋ and K^＋ urinary excretion were observed. When the high-salt diet was administered, systolic blood pressure in the control animals receiving rAAV-LacZ increased from 122.3±1.13 mmHg to a stable 142.4±1.77 mmHg 8 weeks after the high-salt diet. In contrast, there was no significant increase in the blood pressure in the rAAV-HK-treated group, in which the blood pressure remained at 121.9±1.73 mmHg. In the rAAV-HK-treated group, Na^＋ and K^＋ urinary excretion were higher compared to those of the control group. The morphological analysis showed that HK delivery remarkably protected against renal damage induced by a high-salt intake. Conclusion： Our study indicates that rAAV-mediated human tissue kallikrein gene delivery is a potentially safe method for the long-term treatment of hypertension. More importantly, it could be applied in the salt-sensitive population to prevent the occurrence of hypertension.Aim： To investigate the effects of the expression of human kallikrein （HK） on basal level blood pressure and high-salt diet-induced hypertension. Methods： We delivered the recombinant adeno-associated viral （rAAV）-mediated HK （rAAV- HK） gene and rAAV-LacZ （as the control） to normal, adult Sprague-Dawley rats. The animals were administered a normal diet in the first 4 weeks, followed by a high-salt diet. The expression of HK in the rats was assessed by ELISA and RTPCR. Blood pressure and Na^＋ and K^＋ urinary excretion were monitored. Results： Under the normal diet, no obvious changes in blood pressure and Na^＋ and K^＋ urinary excretion were observed. When the high-salt diet was administered, systolic blood pressure in the control animals receiving rAAV-LacZ increased from 122.3±1.13 mmHg to a stable 142.4±1.77 mmHg 8 weeks after the high-salt diet. In contrast, there was no significant increase in the blood pressure in the rAAV-HK-treated group, in which the blood pressure remained at 121.9±1.73 mmHg. In the rAAV-HK-treated group, Na^＋ and K^＋ urinary excretion were higher compared to those of the control group. The morphological analysis showed that HK delivery remarkably protected against renal damage induced by a high-salt intake. Conclusion： Our study indicates that rAAV-mediated human tissue kallikrein gene delivery is a potentially safe method for the long-term treatment of hypertension. More importantly, it could be applied in the salt-sensitive population to prevent the occurrence of hypertension.

关 键 词：recombinant adeno-associated virus vector human tissue kallikrein high-salt diet HYPERTENSION 

分 类 号：R394[医药卫生—医学遗传学] R544.1[医药卫生—基础医学]