Heterogeneity of angiotensin action in renal circulation

Reported concentrations of angiotensin II (Ang II) in renal interstitial fluid are as high as 10 nM. Despite such high concentrations, intrarenal arterial infusion of Ang II at rates that induce far less change in renal Ang II concentration still elicits renal vasoconstriction. We examined whether the glomerular afferent arterioles (Af-Art) was more sensitive to intraluminal than extraluminal Ang II in superficial or juxtamedullary nephrons. Rat superficial Af-Arts with the intact glomerulus were microdissected and perfused in vitro at 70 mmHg, while juxtamedullary Af-Arts were visualized in isolated perfused kidneys (at 100 mm Hg) according to the method of Casellas and Navar. Increasing doses of Ang II (1 pM to 10 nM) or norepinephrine (NE; 1 nM to 1 microM) were added to either bath (extraluminal) or arteriolar perfusate (intraluminal). Decreases in luminal diameter induced by Ang II were significantly larger with intraluminal than extraluminal administration in superficial Af-Art: at 100 pM the diameter decreased by 52 +/- 8% (N = 6) and 7 +/- 3% with intraluminal and extraluminal administration, respectively. In contrast, in the juxtamedullary Af-Arts intraluminal and extraluminal Ang II caused similar constriction. On the other hand, there was no difference in intraluminal versus extraluminal NE action in either superficial or juxtamedullary nephrons. In conclusion, glomerular Af-Arts seem to have a higher sensitivity to luminal than interstitial Ang II in superficial but not juxtamedullary nephrons. Such heterogeneities in Ang II action may be important in the control of glomerular hemodynamics under various physiological and pathological conditions.