K. Yayama et al., KALLIKREIN GENE DELIVERY ATTENUATES HYPERTENSION AND CARDIAC-HYPERTROPHY AND ENHANCES RENAL-FUNCTION IN GOLDBLATT HYPERTENSIVE RATS, Hypertension, 31(5), 1998, pp. 1104-1110
To demonstrate potential therapeutic effects of kallikrein gene delive
ry, we delivered adenovirus (Ad.CMV-cHK) carrying the human tissue kal
likrein gene into two-kidney, one-clip Goldblatt hypertensive rats. A
single intravenous injection of the recombinant adenovirus caused a de
lay of blood pressure increase that began 1 day after injection and co
ntinued for 24 days. A maximal blood pressure reduction was observed i
n rats receiving kallikrein gene delivery compared with control rats r
eceiving Ad.CMV-LacZ (160+/-5 versus 186+/-7 mm Hg, n=6, P<.01). The e
xpression 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 a
nd cardiomyocyte size, as well as an increase in renal blood flow, uri
ne flow, glomerular filtration rates, electrolyte output, and urine ex
cretion, Enhanced renal responses were accompanied by significant incr
eases in urinary kinin, nitrite/nitrate, and cyclic CMP 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.