[Transplantation of atrial natriuretic peptide-expressing fibroblasts reduces blood pressure and increases urine volume in spontaneously hypertensive rats].
To investigate the potential of gene therapy for the treatment of chronic diseases such as hypertension, chronic heart failure, and chronic renal failure, we established the neonatal rat fibroblast line engineered to secrete the mutant human atrial natriuretic peptide (mhANP), and then transplanted the cell line into young spontaneously hypertensive rats (SHR) subcutaneously. We found that a single transplantation of the cell line caused an obvious rise in the concentration of mhANP in serum 7 d after transplantation ((135 +/- 8) vs (106 +/- 7) pg/mL, P < 0.01). The animals' blood pressure in test group was always remarkably lower than that of empty vector group within 42 d after transplantation, even though the blood pressure in all groups was constantly increasing in the process of ontogeny ((175 +/- 10) mm Hg vs (189 +/- 12) mm Hg, P < 0.05). A maximal blood pressure reduction of 33 mm Hg ((157 +/- 9) mm Hg vs (124 +/- 112) mm Hg, P < 0.01) was observed 14 d post cell transplantation. There was a marked increase in urine volume in test group from second week after treatment beginning ((5.9 +/- 0.7) mL/6 h vs (4.3 +/- 0.8) mL/6 h, P < 0.01) and the effect lasted 14 d ((6.1 +/- 1.1) mL/6 h vs (4.0 +/- 0.8) mL/6 h, P < 0.01), however the statistical difference in concentration of K+ and Na+ in serum and urine was not observed. The results suggested that subcutaneous implantation of fibroblasts-expressing mhANP significantly reduced blood pressure in young SHR during the period of ontogeny and efficiently improved their renal function and the somatic gene transfer of mhANP may have potential value in the treatment of human chronic diseases such as hypertension, chronic heart failure, and chronic renal failure.
Li
Tao
T
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Liang
Hongyan
H
Lu
Jinzhi
J
Chen
Weijing
W
Lu
Shengdong
S
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009154:Mutation; D051381:Rats; D011918:Rats, Inbred SHR; D014162:Transfection; D014554:Urination
D009320:Atrial Natriuretic Factor