On the origin of urinary angiotensin II.

Letters to the Editor will be published, if suitable, as space permits. They should not exceed 1000 words (typed double-spaced) in length and may be subject to editing or abridgment. To the Editor: With great interest we read the publication by Shao et al, 1 who propose that angiotensin (Ang) II type 1 (AT 1) receptor stimulation in the kidney results in urinary Ang II excretion. The authors have used an elegant approach, infusing rats with Val 5-Ang II to allow a clear distinction from endogenous Ile 5-Ang II, here denoted as Ang II. Val 5-Ang II is believed to have the same properties as Ang II. We have followed a similar approach and infused 125 I-labeled Ang II in pigs to distinguish it from endogenous Ang II. 2 In these studies, 125 I-Ang II accumulation in the kidney, largely, if not exclusively, depended on AT 1 receptors, as demonstrated by a Ͼ90% reduction in the renal tissue/plasma concentration ratio of 125 I-Ang II after pretreatment with the AT 1 receptor blocker eprosartan. 3 Recent experiments showing low or undetectable renal Ang II levels in AT 1 receptor knockout animals further support the dependency of renal Ang II accumulation on AT 1 receptors. 4 In addition, the porcine renal tissue/plasma concentration ratio of endogenous Ang II decreased by Ϸ90% after eprosartan pretreatment, 3 thus confirming that renal 125 I-Ang II accumulation fully resembles that of endogenous Ang II. In the study by Shao et al, 1 the renal tissue/plasma ratio of endogenous Ang II decreased by Ͼ90% after candesartan treatment (from 358/24 to 21/157), identical to our results in pigs. Yet, the ratio of Val 5-Ang II was virtually unchanged after candesartan treatment (385/283 versus 242/217). This demonstrates that the renal accumulation of Val 5-Ang II, unlike that of Ang II and 125 I-Ang II, largely occurs in an AT 1 receptor– independent manner, at least when infused at a rate of 80 ng/min. One explanation for this discrepancy may be that this rate is above the rate required to obtain (near) complete renal AT 1 receptor occupancy. In agreement with this concept, Val 5-Ang II suppressed plasma renin activity by Ͼ95%. Yet, endogenous plasma Ang II was either unaltered 1 or increased. 5 According to Figure 6, 1 urinary Val 5-Ang II excretion without candesartan amounted to 3 to 7 pmol/24 hours. Urinary volumes ranged from 11 to 38 …