Tubuloglomerular feedback and prolonged ACE-inhibitor treatment in the hypertensive fawn-hooded rat.

Abstract

The spontaneously hypertensive fawn-hooded (FHH) rat develops severe glomerulosclerosis with ageing. The afferent arteriolar resistance is low, resulting in a strongly elevated glomerular capillary pressure (P(GC)). Afferent arteriolar resistance is under the control of the tubuloglomerular feedback (TGF) system, and we studied whether young FHH rats, i.e. at a stage when only mild glomerulosclerosis was present, have diminished TGF responsiveness. Maximum TGF-mediated decreases in stop-flow pressure in response to late proximal perfusion with artificial tubular fluid were 9.0 +/- 1.0 mmHg, a value not different or even slightly lower than observed in normal rats. P(GC) was 59.9 +/- 1.2 mmHg and the estimated P(GC) at half-maximal activation of the TGF system (operating P(GC)) was 54.5 +/- 0.8 mmHg at 11 weeks of age (n = 11), a value higher than observed in normal rats. The second question of the present study concerns the effect of chronic angiotensin-I-converting enzyme inhibitor (ACE-i) administration on P(GC). ACE-i, by reducing angiotensin II (Ang II) availability, diminishes TGF responsiveness, which would offset the beneficial effect on P(GC) under normal flow conditions to the macula densa. Maximum TGF responses were 8.9 +/- 1.0 and 17.5 +/- 1.5 mmHg in 11- and 26-week-old rats that had been treated with the ACE-i lisinopril in the drinking water started when the animals were 7 weeks of age. P(GC) was 44.3 +/- 1.2 (n = 9) and operating P(GC) was 40.1 +/- 1.6 mmHg (n = 9) at 11, values significantly lower than in untreated rats. Values remained lower in the 26-week-old treated animals and were 40.9 +/- 0.8 and 32.6 +/- 1.1 mmHg. (1) the TGF system in this model of spontaneous hypertension and glomerulosclerosis is intact, despite the fact that the FHH rat has a characteristically low afferent arteriolar resistance as compared to other hypertensive rats; (2) the rat displays a normal or even enhanced function of the TGF system following prolonged administration of the ACE-i lisinopril. The latter finding indicates that the reduction of P(GC) achieved by the ACE-i is not offset by a concomitant attenuation of TGF function.