Why the study?
Does tyrosine hydroxylase antisense gene therapy reduce systolic blood pressure in spontaneously hypertensive rats?
Does tyrosine hydroxylase antisense gene therapy reduce systolic blood pressure in spontaneously hypertensive rats?
Antisense gene therapy targeting tyrosine hydroxylase effectively lowers blood pressure and sympathetic activity in a rat model of spontaneous hypertension.
Hypothesis-generating for TH antisense in spontaneous hypertension; requires human trials before clinical consideration.
We investigated the effect of antisense oligodeoxynucleotides (AS ODN) against tyrosine hydroxylase (TH) on hypertension and sympathetic nervous system activity in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) in SHR treated with TH AS ODN (50, 200 microg/rat, i.v.) was significantly lower than that of control SHR. Epinephrine and norepinephrine levels, TH activity, and TH protein levels in the adrenal medulla of SHR were reduced concomitant with TH AS ODN treatment-induced changes in SBP. In contrast, TH AS ODN (200 microg/rat) had no effect on SBP in Wistar-Kyoto rats (WKY), despite significantly decreased catecholamine levels, TH activity, and TH protein levels. These findings suggest that peripheral systemic injection of TH AS ODN may be effective as hypotensive therapy in SHR.
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Kumai et al. (2001) studied this question.
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