Abnormal pressure-natriuresis in transgenic renin gene rats

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.

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.

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.

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)