Renin antisense injected intraventricularly decreases blood pressure in spontaneously hypertensive rats

Brain renin-angiotensin system plays an important role in blood pressure re gulation and is suggested to play a role in the development and maintenance of hypertension. To test the hypothesis that brain renin may play a signif icant role in hypertension in spontaneously hypertensive rats (SHR), phosph orothioated antisense oligodeoxynucleotides targeted to renin mRNA were adm inistered intracerebroventricularly in SHR. Administration of an antisense but not its sense oligodeoxynucleotide produced a prolonged duration of dec rease in blood pressure. Intra-arterial administration of the antisense oli godeoxynucleotide at the same dose that decreased blood pressure when admin istered intraventricularly did not affect blood pressure. Furthermore, reni n mRNA but not angiotensin AT1 receptor mRNA levels were decreased in the h ypothalamus of the antisense oligodeoxynucleotide-treated rats. These resul ts suggest that brain renin may play a significant role in hypertension in SHR. (C) 2001 Elsevier Science Inc.