Acta Pharmacologica Sinica 2008 July; 29 (7): 808-814; doi: 10.1111/j.1745-7254.2008.00815.x

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_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.

Keywords: recombinant adeno-associated virus vector; human tissue kallikrein; high-salt diet; hypertension