Prolonged hypotensive effect of human tissue kallikrein gene delivery and recombinant enzyme administration in spontaneous hypertension rats.
To evaluate the feasibility of treating hypertension by human tissue kallikrein gene (KLK1) delivery and by enzyme (rK1) administration, two recombinant vectors expressing KLK1 cDNA were constructed for gene delivery (pcDNA-KLK1) and recombinant enzyme preparation (pOV-KLK1). Expression of the pcDNA-KLK1 vector in COS-1 cells was confirmed by immunofluorescence and in spontaneous hypertension rats (SHR) by enzymatic detection. Following intramuscular or intravenous injection with the pcDNA-KLK1 vector, systolic pressure of SHR was significantly decreased, which lasted for 20 d to two months depending on dose, route and/or time of injection. Egg white containing recombinant hK1 was prepared by injection of egg-laying hens with the oviduct-specific expression vector pOV-KLK1 and administered into SHR via oral gavage. Following administration, systolic pressure of the SHR was decreased to that of normal rats, which lasted for 3-5 d depending on the dosage used. These data suggest that both hKLK1 gene delivery and recombinant enzyme administration can be used as alternative strategies for treating human hypertension.
Sun
Huaichang
H
Jiangsu Provincial Center for Animal Transgenesis and Biopharming, Yangzhou University Yanhzhou, 225009, PR China. sun78564@hotmail.com
Zhang
Lei
L
Wang
Anping
A
Xue
Zhengfeng
Z
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D019556:COS Cells; D002645:Chickens; D002522:Chlorocebus aethiops; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000628:therapy*; D007022:Hypotension / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D020840:Tissue Kallikreins / Q000235:genetics* / Q000378:metabolism
D011994:Recombinant Proteins; D020840:Tissue Kallikreins