Adenovirus-mediated kallikrein gene delivery reverses salt-induced renal injury in Dahl salt-sensitive rats.
BACKGROUND
The tissue kallikrein-kinin system has been shown to play a role in cardiac and renal functions. In this study, we investigated the ability of kallikrein gene delivery to reverse salt-induced cardiac hypertrophy and renal injury in Dahl salt-sensitive rats.


METHODS
Adenovirus harboring the human tissue kallikrein gene, Ad.CMV-cHK, was delivered intravenously into Dahl salt-sensitive rats suffering from hypertension, cardiac hypertrophy and renal damage induced by a high salt diet (4% NaCl) for four weeks.


RESULTS
Expression of human kallikrein mRNA was detected in rat kidney, heart, aorta and liver, and immunoreactive human kallikrein levels were measured in the serum and urine of rats receiving gene delivery. A single injection of Ad.CMV-cHK caused a significant reduction of blood pressure for more than two weeks. Kallikrein gene transfer caused left ventricular mass reduction and elevated glomerular filtration rate, renal blood flow, urinary excretion, urinary kinin, nitrite/nitrate content, cGMP and cAMP levels. Morphological investigations showed that kallikrein gene transfer caused a significant reversal in salt-induced tissue and organ damage. In the heart, cardiac hypertrophy and fibrosis were reduced, and in the kidney, both glomerular sclerotic lesions and tubular damage were reversed.


CONCLUSIONS
Adenovirus-mediated kallikrein gene delivery is effective in reversing salt-induced cardiac hypertrophy and renal injury in Dahl-salt sensitive rats.
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425-2211, USA. chaol@musc.edu
J
J
Chao
J J
JJ
Zhang
K F
KF
Lin
L
L
Chao
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000628:therapy; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D007610:Kallikreins / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012965:Sodium Chloride / Q000008:administration & dosage
D017931:DNA Primers; D012333:RNA, Messenger; D012965:Sodium Chloride; D007610:Kallikreins