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


CONCLUSIONS
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.
Yan
Jiang-tao
JT
Department of Internal Medicine and Gene Therapy Center, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Wang
Tao
T
Li
Juan
J
Xiao
Xiao
X
Wang
Dao-wen
DW
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*; D007610:Kallikreins / Q000235:genetics* / Q000652:urine; D007668:Kidney / Q000473:pathology; D008297:Male; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012982:Sodium, Dietary
D012982:Sodium, Dietary; D003094:Collagen; D007610:Kallikreins