Hypertension is a polygenic and multifactorial disease and is intimately related to salt homeostasis. Four important vasoactive peptide systems participate in regulating blood pressure and salt homeostasis. Their interplay is indispensible in many physiologic and pathologic conditions. While the renin-angiotensin and the endothelin systems raise blood pressure by inducing vasoconstriction and sodium retention (or excretion), the kallikrein-kinin and the natriuretic peptide systems reduce blood pressure by eliciting vasodilatation and natriuresis. Gene targeting as well as transgenesis have provided us a lot of information on the biological functions of the genes of these systems. Animal models from these technologies are discussed in relation to blood pressure regulation.
Angiotensins ; Animals* ; Blood Pressure* ; Endothelins ; Gene Targeting ; Gene Transfer Techniques ; Homeostasis ; Hypertension ; Models, Animal* ; Natriuresis ; Sodium ; Vasoconstriction ; Vasodilation

Endothelin-1 (ET-1) is unequivocally elevated in the kidney with ischemic acute renal failure (ARF), whereas ET receptors (ET(A)R and ET(B)R) are variably expressed. Although renal functional and structural changes are similar between ischemic and nephrotoxic ARF, there are few reports on the alteration in the ET system in nephrotoxic ARF. This study was, therefore, undertaken to investigate changes in renal expression of ET-1 and its receptors in nephrotoxic ARF induced by cisplatin. Mice were intraperitoneally injected with 16 mg of cisplatin/kg at a single dose, and the expression of mRNA and protein was then quantified by real-time RT-PCR and Western blot, respectively. Immunohistochemistry was conducted for localization. Three days after treatment, ET-1 transcript in cisplatin- treated mice was thirteen times higher than that in controls, whereas ET-1 peptide was increased by 1.5-fold. Cisplatin caused a 2-fold increase in the levels of ET(A)R mRNA and protein. Most of the increased immunoreactive ET-1 and ET(A)R were localized in damaged tubules. Neither the expression of ET(B)R mRNA nor the abundance and immunoreactive level of ET(B)R protein were changed. The findings suggest that the individual components of the renal ET system are differentially regulated in cisplatin-induced nephrotoxic ARF.
Acute Kidney Injury ; Animals ; Blotting, Western ; Cisplatin ; Endothelin-1 ; Endothelins ; Immunohistochemistry ; Kidney ; Mice ; Receptors, Endothelin ; RNA, Messenger