Adenovirus-mediated human prostasin gene delivery is linked to increased aldosterone production and hypertension in rats.
Prostasin has been demonstrated to be an activator of epithelial sodium channels in cultured renal and bronchial epithelial cells. In this study, we evaluated the effects of adenovirus-mediated gene transfer of human prostasin on blood pressure regulation and sodium reabsorption in Wistar rats. Expression of human prostasin mRNA was identified in rat adrenal gland, liver, kidney, heart, lung, and aorta, and immunoreactive human prostasin was detected in the circulation and urine of rats receiving prostasin gene transfer. A single injection of adenovirus carrying the prostasin gene caused prolonged increases in blood pressure for 3-4 wk. Blood pressure increase was accompanied by elevated plasma aldosterone levels and reduced plasma renin activity. The increase in blood pressure and plasma aldosterone levels as well as the reduction of plasma renin activity correlated with the expression of human prostasin transgene. Elevated plasma aldosterone levels were detected at 3 days after gene transfer before the development of hypertension, indicating that stimulation of mineralocorticoid production is the primary target of prostasin. Prostasin gene transfer significantly reduced urinary K(+) excretion but increased urinary Na(+) and kallikrein excretion. Elevated renal kallikrein levels promote natriuresis, which may lead to sodium escape and prevent further increases of blood pressure after prostasin gene transfer. In summary, these results suggest that prostasin participates in blood pressure and electrolyte homeostasis by regulating the renin-angiotensin-aldosterone and kallikrein-kinin systems.
Wang
Cindy
C
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425-2211, USA. wangxi@musc.edu
Chao
Julie
J
Chao
Lee
L
D000256:Adenoviridae / Q000235:genetics*; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D008297:Male; D011188:Potassium / Q000652:urine; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D014882:Water-Electrolyte Balance; D000099271:Prostasin
D000450:Aldosterone; D011188:Potassium; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D000099271:Prostasin