Renin antisense injected intraventricularly decreases blood pressure in spontaneously hypertensive rats.
Brain renin-angiotensin system plays an important role in blood pressure regulation and is suggested to play a role in the development and maintenance of hypertension. To test the hypothesis that brain renin may play a significant role in hypertension in spontaneously hypertensive rats (SHR), phosphorothioated antisense oligodeoxynucleotides targeted to renin mRNA were administered intracerebroventricularly in SHR. Administration of an antisense but not its sense oligodeoxynucleotide produced a prolonged duration of decrease in blood pressure. Intra-arterial administration of the antisense oligodeoxynucleotide at the same dose that decreased blood pressure when administered intraventricularly did not affect blood pressure. Furthermore, renin mRNA but not angiotensin AT1 receptor mRNA levels were decreased in the hypothalamus of the antisense oligodeoxynucleotide-treated rats. These results suggest that brain renin may play a significant role in hypertension in SHR.
Kubo
T
T
Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo, Japan. kubo@ac.shouaku.ac.jp
Ikezawa
A
A
Kambe
T
T
Hagiwara
Y
Y
Fukumori
R
R
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics; D012083:Renin / Q000235:genetics*
D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D012083:Renin