Candesartan normalizes exaggerated tubuloglomerular feedback activity in young spontaneously hypertensive rats

This study examines the effect of systemic blockade of angiotensin II AT1 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 pressure (SFP) and early proximal flow rate (EPFR) measurements during perfusion of 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 addition, EPFR at a high perfusion rate (40 nl/min) was lower in SHR, indicating exaggerated TGF activity. Blockade of AT1 receptors was achieved by intravenous injection of 0.05 mg/kg candesartan, which did not affect mean arterial pressure. Renal blood flow and mean arterial pressure responses to injections of angiotensin II were blocked by >95%. Maximum SFP response in SHR decreased 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) decreased from -5.5 to -2.0 mmHg/nl per min. In contrast, maximum SFP response and TGF reactivity were unchanged by AT1 receptor blockade in euvolemic WKY. A small effect was noted as an increase in turning point to 18.0 nl/min after candesartan treatment. Thus, the exaggerated TGF activity in young SHR is markedly attenuated by systemic administration of candesartan, whereas TGF was basically unchanged in euvolemic WKY. These results demonstrate that angiotensin II plays an important role in the enhanced TGF activity observed in young SHR. Significant TGF activity, essentially at normal levels for euvolemic animals, persists during AT1 receptor blockade in both groups of rats.