title: Prolonged hypotensive effect of human tissue kallikrein gene delivery and recombinant enzyme administration in spontaneous hypertension rats.
abstract: 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.
authors.affiliation: Jiangsu Provincial Center for Animal Transgenesis and Biopharming, Yangzhou University Yanhzhou, 225009, PR China. sun78564@hotmail.com
authors.forename: Huaichang
authors.initials: H
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Anping
authors.initials: A
authors.lastname: Wang
authors.forename: Zhengfeng
authors.initials: Z
authors.lastname: Xue
mesh_terms: 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
chemical_list: D011994:Recombinant Proteins; D020840:Tissue Kallikreins