TUBULOGLOMERULAR FEEDBACK AND PROLONGED ACE-INHIBITOR TREATMENT IN THE HYPERTENSIVE FAWN-HOODED RAT

Background. The spontaneously hypertensive fawn-hooded (FHH) rat devel ops severe glomerulosclerosis with ageing. The afferent arteriolar res istance is low, resulting in a strongly elevated glomerular capillary pressure (P-GC). Methods. 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 glomerulosclero sis was present, have diminished TGF responsiveness. Results. Maximum TGF-mediated decreases in stop-flow pressure in response to late proxi mal perfusion with artificial tubular fluid were 9.0+/-1.0 mmHg, a val ue 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 activa tion of the TGF system (operating P-GC) was 54.5+/-0.8 mmHg at 11 week s of age (n=11), a value higher than observed in normal rats. The seco nd question of the present study concerns the effect of chronic angiot ensin-I-converting enzyme inhibitor (ACE-i) administration on P-GC. AC E-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 wer e 8.9+/-1.0 and 17.5+/-1.5 mmHg in 11- and 26-week-old rats that had b een treated with the ACE-i lisinopril in the drinking water started wh en the animals were 7 weeks of age. P-GC was 44.3+/-1.2 (n= 9) and ope rating P-GC was 40.1+/-1.6 mmHg (n=9) at 11, values significantly lowe r than in untreated rats. Values remained lower in the 26-week-old tre ated animals and were 40.9+/-0.8 and 32.6+/-1.1 mmHg. Conclusions. (1) the TGF system in this model of spontaneous hypertension and glomerul osclerosis is intact, despite the fact that the FHH rat has a characte ristically low afferent arteriolar resistance as compared to other hyp ertensive rats; (2) the rat displays a normal or even enhanced functio n of the TGF system following prolonged administration of the ACE-i li sinopril. The latter finding indicates that the reduction of P-GC achi eved by the ACE-i is not offset by a concomitant attenuation of TGF fu nction.