ROLE OF NITRIC-OXIDE IN MODULATING THE VASOCONSTRICTOR ACTIONS OF ANGIOTENSIN-II IN PREGLOMERULAR AND POSTGLOMERULAR VESSELS IN DOGS

The purpose of this study was to determine the role of nitric oxide in modulating the vasoconstrictor effect of angiotensin II (Ang II) on renal segmental resistances in the dog. To achieve this objective we examined the effect of intrarenal infusions of Ang II on preglomerular and postglomerular resistances in the presence and absence of intrarenal nitric oxide synthesis inhibition established by an intrarenal infusion of N-G-nitro-L-arginine-methyl ester at 5 mu g/kg per minute in dogs. The whole-kidney stop-flow technique was used. Renal artery pressure was servo-controlled at 78+/-2 mm Hg throughout the study. Intrarenal infusion of Anq II alone at 0.5 and 2.0 ng/kg per minute increased renal vascular resistance (Delta 0.064+/-0.011 and Delta 0.171+/-0.030 mm Hg/mL per minute, respectively) and decreased renal blood flow (Delta 21+/-4 and Delta 45+/-9 mL/min). Associated with these changes, glomerular hydrostatic pressure and preglomerular resistance increased slightly (Delta 1.1+/-0.9 and Delta 1.6+/-1.8 mm Hg; Delta 0.008+/-0.005 and Delta 0.030+/-0.010 mm Hg/mL per minute, respectively), and postglomerular resistance increased markedly (Delta 0.046+/-0.011 and Delta 0.116+/-0.026 mm Hg/mL per minute). When dogs were pre-treated with an intrarenal infusion of the nitric oxide synthesis blocker, Ang II at 0.5 and 2.0 ng/kg per minute increased renal vascular resistance (Delta 0.27+/-0.058 and Delta 1.088+/-0.242 mm Hg/mL per minute) and decreased renal blood flow (Delta 28+/-5 and Delta 62+/-9 mL/min). However, in sharp contrast to vehicle pretreatment, Ang II decreased glomerular hydrostatic pressure (Delta 3.4+/-1.5 and Delta 9.9+/-2.0 mm Hg), increased postglomerular resistance (Delta 0.122+/-0.029 and Delta 0.439+/-0.133 mm Hg/mL per minute), and increased preglomerular resistance (Delta 0.109+/-0.031 and Delta 0.487+/-0.099 mm Hg/mL per minute) in dogs pretreated with the nitric oxide synthesis inhibitor. In summary, these data indicate that during vehicle treatment Ang II infusion in the stop-flow kidney had a predominant effect on postglomerular resistance. However, when nitric oxide synthesis was blocked, Ang II had a profound effect on preglomerular resistance. These findings suggest that nitric oxide may play an important role in protecting mainly preglomerular vessels and to a lesser extent postglomerular vessels from Ang II-induced renal vasoconstriction in dogs.