Kallikrein Gene Delivery Attenuates Hypertension and Cardiac Hypertrophy and Enhances Renal Function in Goldblatt Hypertensive Rats
作者:
Katsutoshi Yayama,
Cindy Wang,
Lee Chao,
Julie Chao,
期刊:
Hypertension
(OVID Available online 1998)
卷期:
Volume 31,
issue 5
页码: 1104-1110
ISSN:0194-911X
年代: 1998
出版商: OVID
数据来源: OVID
摘要:
To demonstrate potential therapeutic effects of kallikrein gene delivery, we delivered adenovirus (Ad.CMV-cHK) carrying the human tissue kallikrein gene into two-kidney, one-clip Goldblatt hypertensive rats. A single intravenous injection of the recombinant adenovirus caused a delay of blood pressure increase that began 1 day after injection and continued for 24 days. A maximal blood pressure reduction was observed in rats receiving kallikrein gene delivery compared with control rats receiving Ad.CMV-LacZ (160 +/- 5 versus 186 +/- 7 mm Hg, n=6, P<.01). The expression of human tissue kallikrein mRNA was identified in the kidney, heart, aorta, and liver of rats receiving kallikrein gene delivery. Immunoreactive human kallikrein levels were measured in rat serum and urine in a time-dependent manner. Adenovirus-mediated kallikrein gene delivery caused a significant reduction in the left ventricular mass and cardiomyocyte size, as well as an increase in renal blood flow, urine flow, glomerular filtration rates, electrolyte output, and urine excretion. Enhanced renal responses were accompanied by significant increases in urinary kinin, nitrite/nitrate, and cyclic GMP levels. These findings show that the expression of human tissue kallikrein via gene delivery has protective effects against renovascular hypertension and cardiovascular and renal dysfunction. (Hypertension. 1998;31:1104-1110.)
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