Abnormal pressure-natriuresis in transgenic renin gene rats.

Objective: Pressure-diuresis-natriuresis relationships were compared in rats made transgenic by implantation of the mouse salivary gland renin gene [TGR(mRen-2)27 rats] and Sprague-Dawley/Hannover rats to determine whether resetting of renal function contributes to the development of hypertension in these rats.

Methods: Differences in the neural and hormonal background were minimized by denervating the kidney and holding plasma vasopressin, aldosterone, cortisol and norepinephrine levels constant by intravenous infusion.

Results: In Hannover rats (n = 9), urine flow and sodium excretion increased from 26.4 +/- 6.2 to 86.8 +/- 8.6 microliters/min per g kidney weight and from 5.1 +/- 0.8 to 15.3 +/- 1.0 mumol/min per g kidney weight as renal perfusion pressure (RPP) was increased from 107 to 153 mmHg. The renal blood flow (RBF) and glomerular filtration rate (GFR) were well-autoregulated and averaged 6.6 and 1.5 ml/min per g kidney weight throughout the range of pressures studied. In TGR (n = 10), urine flow and sodium excretion increased from 30.0 +/- 6.1 to 59.7 +/- 7.2 microliters/min per g kidney weight and from 3.8 +/- 0.9 to 8.5 +/- 1.3 mumol/min per g kidney weight in response to an elevation in RPP from 170 to 212 mmHg. The RBF and GFR were about 20% lower in TGR than in Hannover rats and averaged 4.1 and 1.0 ml/min per g kidney weight, respectively.

Conclusions: The results show that the pressure-diuresis-natriuresis relationship is shifted to higher pressure levels in TGR and that this is associated with enhanced tubular reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)