Muscle delivery of human kallikrein gene reduces blood pressure in hypertensive rats.
We recently found that transgenic mice expressing human tissue kallikrein develop sustained hypotension. The result suggests that a continuous supply of human tissue kallikrein could have a prolonged effect on blood pressure reduction. In the present study, we investigated the potential of using human tissue kallikrein for gene therapy by injecting a kallikrein gene construct into the skeletal muscle of spontaneously hypertensive rats. Expression of the human tissue kallikrein messenger RNA in spontaneously hypertensive rats was identified by reverse transcription-polymerase chain reaction with Southern blot. Human tissue kallikrein was detected in the injected animals by an enzyme-linked immunosorbent assay. Injection of the human kallikrein gene into spontaneously hypertensive rats caused a significant reduction of systemic blood pressure, ranging from 15 to 26 mm Hg, compared with the control group. The differences were significant 1 week after the injection and continued for more than 2 months. Blood pressure reduction could be reversed after the administration of the bradykinin antagonist Hoe 140. The results indicate that somatic delivery of the human tissue kallikrein gene induces a sustained reduction of systemic blood pressure in spontaneously hypertensive rats. The present study raises the possibility of applying kallikrein gene therapy to the treatment of human hypertensive diseases.
Xiong
W
W
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425, USA.
Chao
J
J
Chao
L
L
D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure; D015316:Genetic Therapy / Q000379:methods*; D006973:Hypertension / Q000503:physiopathology* / Q000628:therapy*; D007273:Injections, Intramuscular; D007610:Kallikreins / Q000235:genetics*; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D014158:Transcription, Genetic
D015335:Molecular Probes; D012333:RNA, Messenger; D007610:Kallikreins