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

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.

• Authors: Jiang-tao Yan, Tao Wang, Juan Li, Xiao Xiao, Dao-wen Wang
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 29 Issue 7 Pg. 808-14 (Jul 2008) ISSN: 1745-7254 [Electronic] United States
• PMID: 18565278 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sodium, Dietary
• Collagen
• Kallikreins

Topics

• Adenoviridae (genetics)
• Animals
• Blood Pressure (physiology)
• Collagen (metabolism)
• Genetic Therapy
• Humans
• Hypertension (chemically induced, pathology, therapy)
• Kallikreins (genetics, urine)
• Kidney (pathology)
• Male
• Plasmids (genetics)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Sodium, Dietary