Central delivery of human tissue kallikrein gene reduces blood pressure in hypertensive rats.
The human tissue kallikrein gene, in the form of naked DNA (CMV-cHK) or an adenoviral vector (Ad.CMV-cHK), was directly delivered by intracerebroventricular injection into spontaneously hypertensive rats. Control rats received the same amount of vector DNA (pcDNA3) or adenoviral vector (Ad.CMV-LacZ) carrying the lacZ gene. A single injection of the human tissue kallikrein gene caused a rapid and prolonged blood pressure-lowering effect that began 1 day post injection and the effect lasted for more than 7 days. The expression of human tissue kallikrein and its mRNA was identified in the cortex, cerebellum, brain stem, hippocampus and hypothalamus. Cellular localization of beta-galactosidase was detected by X-gal staining in the thalamus, hypothalamus and third ventricle in rats injected with Ad.CMV-LacZ. This suggests that the tissue kallikrein-kinin system may function in the central control of blood pressure homeostasis.
Wang
C
C
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425-2211, USA.
Chao
C
C
Madeddu
P
P
Chao
L
L
Chao
J
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D015870:Gene Expression; D005822:Genetic Vectors; D006706:Homeostasis; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology* / Q000517:prevention & control; D007276:Injections, Intraventricular; D007610:Kallikreins / Q000235:genetics* / Q000502:physiology*; D007763:Lac Operon; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D011994:Recombinant Proteins; D004247:DNA; D001616:beta-Galactosidase; D007610:Kallikreins