L‐arginine uptake mechanisms and responses of intrarenal perfusion to angiotensin II

The roles of L‐arginine uptake mechanisms in responses of intrarenal perfusion to angiotensin II were examined in anaesthetized male Sprague‐Dawley rats. A transonic flow probe was used to measure total renal perfusion (RBF) and laser Doppler probes were used to measure renal cortical perfusion (CBF) and medullary perfusion (MBF). Mean arterial pressure (MAP) was maintained at a constant level. In the first group of rats (n = 7), responses of MAP, RBF, CBF and MBF to angiotensin II (10 and 100 ng/kg/min; iv; 10 min each) were recorded under control conditions, after L‐lysine (5 mg/kg/min, 20 min, iv) and subsequently after L‐arginine (10 mg/kg/min, 20 min, iv). We have previously shown that L‐lysine blocks cellular L‐arginine uptake in the kidney. A control group of rats received saline (1 ml/kg/min) instead of L‐lysine and L‐arginine (n = 6). Under control conditions, angiotensin II reduced RBF (−14 ± 6% and–42 ± 8% at 10 and 100 ng/kg/min, respectively) and CBF (−12 ± 3% and −21 ± 7%) but had little effect on MBF (7 ± 9% and 7 ± 11%). Saline vehicle had little effect on baseline levels of RBF, CBF or MBF, or on renal responses to angiotensin II. Neither L‐lysine nor Lsarginine affected baseline levels of RBF, CBF or MBF. L‐lysine enhanced RBF (−28 ± 3% and −56 ± 4%; P = 0.02) and CBF (−19 ± 3% and −36 ± 4%; P = 0.02) but not MBF responses to angiotensin II. L‐arginine blunted the RBF response (−15 ± 6% and −39 ± 9 %; P = 0.04), and tended to blunt the CBF response (−10 ± 3% and −14 ± 7%; P = 0.06) to angiotensin II. L‐arginine uptake mechanisms seem to be vital in blunting angiotensin II induced reductions in CBF but not MBF. This phenomenon could play a key role in long‐term blood pressure regulation. Research support: HL‐29587