Tyrosine hydroxylase antisense gene therapy causes hypotensive effects in the spontaneously hypertensive rats

We investigated the effect of antisense oligodeoxynucleotides (AS ODN) agai nst tyrosine hydroxylase (TH) on hypertension and sympathetic nervous syste m activity in spontaneously hypertensive rats (SHR). Systolic blood pressur e (SBP) in SHR treated with TH AS ODN (50,200 mug/rat, i.v.) was significan tly lower than that of control SHR. Epinephrine and norepinephrine levels, TH activity, and TH protein levels in the adrenal medulla of SHR were reduc ed concomitant with TH AS ODN treatment-induced changes in SBP. In contrast , TH AS ODN (200 mug/rat) had no effect on SBP in Wistar-Kyoto rats (WKY), despite significantly decreased catecholamine levels, TH activity, and TH p rotein levels. These findings suggest that peripheral systemic injection of TH AS ODN may be effective as hypotensive therapy in SHR. (C) 2001 Lippinc ott Williams & Wilkins.