Abstract
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 ELIS A and RT-PCR. 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.
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This study was supported by grants from National Natural Science Foundation Committee (No 30571841), National 863 project (No 2006AA02A406), 973 project (No 2007CB512004).
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Yan, Jt., Wang, T., Li, J. et al. Recombinant adeno-associated virus-mediated human kallikrein gene therapy prevents high-salt diet-induced hypertension without effect on basal blood pressure. Acta Pharmacol Sin 29, 808–814 (2008). https://doi.org/10.1111/j.1745-7254.2008.00815.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00815.x
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