ENDOTHELIN IN THE KIDNEY IN MALIGNANT PHASE HYPERTENSION

A role for endothelin in malignant phase hypertension has been suggest ed on the basis of reported increases of circulating plasma immunoreac tive endothelins in animal models. Recently, a hypertensive rat model that exhibits a genetically determined tendency for developing spontan eous onset malignant hypertension has been described. Expression of th e three genes endothelin-1, endothelin-2, and endothelin-3 was quantif ied in the kidney by specific RNase protection assays in rats with est ablished malignant hypertension, in rats with benign hypertension with and without a genetic susceptibility to malignant hypertension, and i n normotensive Sprague-Dawley rats. Endothelin-1 mRNA levels were sign ificantly elevated in the group with malignant hypertension compared w ith the other three groups. For determination of whether endothelin-1- mediated effects were crucial in the transition from benign to maligna nt phase hypertension, an oral nonspecific combined endothelin-A and e ndothelin-B receptor antagonist (bosentan) was given to hypertensive r ats susceptible to malignant hypertension. No hypotensive effects were observed, and no significant difference in the incidence of malignant hypertension was observed between treated and control groups. In conc lusion, although increased endothelin-1 mRNA expression was found in k idney tissue from rats developing malignant hypertension, blockade of endothelin-1-mediated effects did not prevent the transition from beni gn phase hypertension. Hence, increased renal endothelin-1 expression in this model of malignant hypertension does not appear to have a caus ative role and may simply reflect cellular damage and ischemia.