Exp Mol Med.  2004 Feb;36(1):23-27.

Prolonged hypotensive effect of human tissue kallikrein gene delivery and recombinant enzyme administration in spontaneous hypertension rats

• Sun H
• Zhang L
• Wang A
• Xue Z

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.

Keyword

gene delivery; human tissue kallikrein; hypotensive effect; recombinant enzyme administration

MeSH Terms

Animals
Blood Pressure/physiology
COS Cells
Cercopithecus aethiops
Chickens
Female
Gene Therapy
*Gene Transfer Techniques
Genetic Vectors/genetics/metabolism
Humans
Hypertension/genetics/*therapy
Hypotension/genetics/*metabolism
Rats
Rats, Inbred SHR
Recombinant Proteins/administration & dosage/genetics/metabolism/*therapeutic use
Tissue Kallikreins/*genetics/metabolism