20 Years of hypertension research using genetically modified animals: no clinically promising approaches in sight.

The incidence of essential or primary hypertension is increasing, especially in the northern hemisphere, but although the disease displays clear symptoms, its aetiology appears very complex, and thus no causal treatment is available yet. In the 1990's, genetically modified animals (GMO) were considered to be the key to solving this problem of high complexity. However, until now, although a few approaches have shown that old, well-known drugs have a positive effect (decrease of blood pressure) on such animal models of hypertension, no approach has appeared in the literature of this area of research which might indicate a direct connection between GMO and a therapeutic strategy to treat or prevent this type of hypertension in humans. Instead, criticism of the GMO approach has accumulated in the last years, arguing that it is misleading as this disease does not have a monogenic cause and so complementary regulatory mechanisms could prevent the true identification of the function of the modified genes. Furthermore, the technology is best developed in mice, whose physiology of blood pressure is different from that of humans. Because of species specificity, it is not easy to extrapolate the results from animal models of hypertension to human hypertension. Also, in the years 2000 to 2004 a reorientation of the technology and the aims of this kind of research took place. Therefore, although these approaches are without exception deemed "very promising" in the literature, it cannot be expected that research on GMO will make any contribution to a new therapeutic strategy in the near future.