Candesartan normalizes exaggerated tubuloglomerular feedback activity in young spontaneously hypertensive rats

This study examines the effect of systemic blockade of angiotensin II AT(1) receptors by candesartan on the exaggerated tubuloglomerular feedback (TGF ) activity in 7-wk-old, euvolemic spontaneously hypertensive rats (SHR) and in Wistar-Kyoto rats (WKY). TGF activity was assessed by stop-flow pressur e (SFP) and early proximal flow rate (EPFR) measurements during perfusion o f Henle's loop. During the control period, SHR exhibited a greater maximal SFP response (19 versus 0.11 mmHg), and a lower tubular flow rate elicited half-maximal response (turning point) (12.7 versus 14.1 nl/min). In additio n, EPFR at a high perfusion rate (40 nl/min) was lower in SHR, indicating e xaggerated TGF activity. Blockade of AT(1) receptors was achieved by intrav enous injection of 0.05 mg/kg candesartan, which did not affect mean arteri al pressure. Renal blood flow and mean arterial pressure responses to injec tions of angiotensin II were blocked by >95%. Maximum SFP response in SHR d ecreased to 11 mmHg, and turning point increased to 16.5 nl/min. The slope of the TGF response curve at the half-maximal SFP response (reactivity) dec reased from -5.5 to -2.0 mmHg/nl per min. In contrast, maximum SFP response and TGF reactivity were unchanged by AT(1) receptor blockade in euvolemic WKY. A small effect was noted as an increase in turning point to 18.0 nl/mi n after candesartan treatment. Thus, the exaggerated TGF activity in young SHR is markedly attenuated by systemic administration of candesartan, where as TGF was basically unchanged in euvolemic WKY. These results demonstrate that angiotensin II plays an important role in the enhanced TGF activity ob served in young SHR. Significant TGF activity, essentially at normal levels for euvolemic animals, persists during AT(1) receptor blockade in both gro ups of rats.