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  • Title: Recombinant adeno-associated virus-mediated human kallikrein gene therapy prevents high-salt diet-induced hypertension without effect on basal blood pressure.
    Author: Yan JT, Wang T, Li J, Xiao X, Wang DW.
    Journal: Acta Pharmacol Sin; 2008 Jul; 29(7):808-14. PubMed ID: 18565278.
    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 ELISA 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-HKtreated 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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