Effects of Losartan, a nonpeptide angiotensin II receptor antagonist, on norepinephrine overflow and antidiuresis induced by stimulation of renal nerves in anesthetized dogs.

We examined the role of endogenous angiotensin II on renal noradrenergic neurotransmission in anesthetized dogs, using Losartan, a nonpeptide angiotensin II receptor (angiotensin subtype 1) antagonist. The renal nerve stimulation caused a frequency-dependent increase in renal norepinephrine secretion rate. The low frequency renal nerve stimulation (0.5-2.0 Hz) significantly decreased urine flow and urinary excretion of sodium, without affecting renal hemodynamics. The high frequency renal nerve stimulation (2.5-5.0 Hz) produced a more potent antidiuresis and a renal vasoconstriction that resulted in reductions of renal blood flow and glomerular filtration rate. Intrarenal arterial infusion of Losartan (10 and 100 micrograms/kg/min) did not affect the basal levels of norepinephrine secretion rate, although increased urine formation with some renal vasodilation were observed during infusion of the drug. The administration of Losartan had an inhibitory action on the decreased urine formation, renal vasoconstriction and enhanced norepinephrine secretion rate, in response to renal nerve stimulation. Based on these findings, we suggest that endogenous angiotensin II seems to regulate renal noradrenergic neurotransmission by facilitating norepinephrine release, through the prejunctional angiotensin subtype 1 receptor.