PROXIMAL TUBULAR FLUID, KIDNEY, AND PLASMA-LEVELS OF ANGIOTENSIN-II IN HYPERTENSIVE REN-2 TRANSGENIC RATS

The present study was performed to assess the plasma and kidney levels of angiotensin I (ANG I) and ANG II during prehypertensive (4- to 5-w k old), development (6- to 8-wk old), and maintenance (10- to 12-wk ol d) phases of hypertension in pentobarbital-anesthetized transgenic rat s [TGR; strain name: TGR(mRen2)27] and age-matched transgene-negative Hannover Sprague-Dawley rats (HanSD). At 4-5 wk, mean arterial pressur es of TGR were not different from those of HanSD (110 +/- 5 vs. 114 +/ - 4 mmHg). However, mean arterial pressures of 6-8 wk and 10-12 wk TGR were higher than those of HanSD (179 +/- 3 vs. 110 +/- 6 and 173 +/- 5 vs. 116 +/- 3 mmHg, respectively; P < 0.01 in both cases). Plasma AN G II levels in 4-5 wk and 6-8 wk TGR were not different from those in HanSD (70 +/- 11 vs. 86 +/- 7 and 60 +/- 8 vs. 48 +/- 12 fmol/ml, resp ectively). However, plasma ANG II levels in 10-12 wk TGR were higher t han those in HanSD (125 +/- 26 vs. 38 +/- 12 fmol/ml, P < 0.01). Kidne y ANG II levels in 4-5 wk, 6-8 wk, and 10-12 wk TGR averaged 370 +/- 5 7, 247 +/- 16, and 562 +/- 86 fmol/g, respectively, values not differe nt from those in HanSD. In additional studies performed on 6-8 wk TGR and HanSD, multiple free-flow proximal tubular fluid collections were obtained and pooled for each animal. In these experiments, mean arteri al pressures of the 10 TGR and 7 HanSD studied averaged 178 +/- 9 and 129 +/- 3 mmHg (P < 0.01), respectively. The ANG II concentration in p roximal tubular fluid obtained from TGR averaged 5.6 +/- 2.1 pmol/ml ( n = 10), a value not different from that in proximal tubular fluid col lected from HanSD (5.3 +/- 2.8 pmol/ml, n = 7). However, the ANG II co ntents of the micropunctured left kidney and the nonmicropunctured rig ht kidney of TGR were lower than those in HanSD (690 +/- 95 vs. 1,374 +/- 210 and 659 +/- 119 vs. 1,303 +/- 196 fmol/g, respectively; P < 0. 01 in both cases). The present findings indicate that proximal tubular fluid of hypertensive TGR contains nanomolar concentrations of ANG II and that proximal tubular fluid, plasma and kidney ANG II levels in a nesthetized hypertensive TGR are not markedly suppressed compared with those in normotensive control rats.