TRANSGENIC ANIMAL-MODELS FOR THE FUNCTIONAL-ANALYSIS OF VASOACTIVE PEPTIDES

The interplay of vasoactive peptide systems is an essential determinan t of blood pressure regulation in mammals. While the endothelin and th e renin-angiotensin systems raise blood pressure by inducing vasoconst riction and sodium retention, the kallikrein-kinin and the natriuretic -peptide systems reduce arterial pressure by eliciting vasodilatation and natriuresis. Transgenic technology has proven to be very useful fo r the functional analysis of vasoactive peptide systems. As an outstan ding example, transgenic rats overexpressing the mouse Ren-2 renin gen e in several tissues become extremely hypertensive. Several other tran sgenic rat and mouse strains with genetic modifications of components of the renin-angiotensin system have been developed in the past decade . Moreover, in recent years gene-targeting technology was employed to produce mouse strains lacking these proteins. The established animal m odels as well as the main insights gained by their analysis are summar ized in this review.