Central Antisense Treatment Against Thyroliberin Normalizes Blood Pressure in Spontaneously Hypertensive Rats Without Affecting Thyroid Status.
Thyroliberin (TRH) participates in central cardiovascular regulation and hypothalamic TRH precursor gene overexpression induces hypertension which can be reversed by antisense (AS) treatment. SHR show an increased central TRH synthesis and release and TRH receptor number. We show here that a phosphotioate AS against the preTRH injected icv decreased the augmented diencephalic TRH content (ng/mg protein) along with a normalization of systolic blood pressure (SABP) at 24-48 hs in SHR without effect in normotensive WKY rats (table). Saline or sense treatment had no effects. To investigate if changes in thyroid function may explain these results, we studied plasma TSH, T3 (ng/ml) and T4 (ug%) in control (CON) and AS-treated WKY and SHR. Although TSH was elevated in SHR compared to WKY rats in basal conditions and AS reverted it (table), no differences (n=5) were observed between strains with or without AS treatment in plasma T4 (CON; WKY: 5.0±0.4 vs SHR: 5.3±0.5 and AS; WKY:5.4±0.3 vs SHR: 5.6±0.4) or T3 (CON; WKY: 1.3±0.4 vs SHR: 1.1±0.2 and AS; WKY: 1.5±0.2 vs SHR: 1.4±0.3). To summarize, TRH AS decreases the higher diencephalic TRH content and changed arterial blood pressure to that of WKY rats even though SHR were basally and after AS treatment remained clinically euthyroid. These results suggest that the central TRH system is involved in the etiopathogenesis of hypertension in this model.