LIFELONG ANGIOTENSIN-CONVERTING ENZYME-INHIBITION, PRESSURE NATRIURESIS, AND RENIN-ANGIOTENSIN SYSTEM GENE-EXPRESSION IN TRANSGENIC (MREN-2)27 RATS

The transgenic rat (TGR) (mRen-2)27 is said to have low circulating ac tive renin values in plasma and little or no renin gene expression in the kidney. Nevertheless, intrarenal angiotensin Ii-related effects ap pear to be responsible for the rightward shift in pressure-natriuresis curves of TGR. To clarify the role of the intrarenal renin-angiotensi n system in modulating TGR pressure-natriuresis, TGR were given lifelo ng lisinopril by treating TGR and their mothers before conception, Rat and mouse renin, AT, receptor, and angiotensinogen gene expression in the kidneys were studied with in situ hybridization. Neural and endoc rine regulatory differences between TGR and Sprague-Dawley Hannover (S DH) rats were eliminated by renal denervation and infusion of vasopres sin, aldosterone, 17-OH corticosterone, and norepinephrine, TGR with l isinopril had blood pressures similar to SDH. In TGR with lisinopril, the pressure-natriuresis curve was shifted leftward but not quite to t he values observed in SDH given lisinopril, The histology of lisinopri l-treated TGR was indistinguishable from normal SDH, Lisinopril increa sed rat renin and angiotensinogen gene expression both in SDH and TGR, but it did not influence mouse renin gene expression in TGR. Disconti nuing lisinopril increased blood pressure in TGR and shifted the press ure-natriuresis relationship rightward, Thus, the components of the en dogenous renin-angiotensin system and the mouse renin transgene were p resent and expressed in kidneys of TGR, The rat gene components respon ded to lisinopril as expected, but the mouse renin transgene expressio n was not influenced. Lisinopril normalized TGR blood pressure: howeve r, a detectable leftward shift in pressure-natnuresis remained. These studies underscore the role of angiotensin-mediated effects of the mou se renin transgene in terms of shifting pressure-natriuresis in TGR.