Role of kinins in the control of renal papillary blood flow, pressure natriuresis, and arterial pressure

The present study evaluated the effects of blocking kinins with the bradykinin B-2 receptor antagonist Hoe140 on the relationship between renal perfusion pressure, papillary blood flow (PBF), and sodium excretion. To determine the relevance of renal kinins in the long-term control of arterial pressure, the effect of a chronic intrarenal infusion of Hoe140 on arterial pressure and sodium balance was also studied. PBF was not autoregulated in volume-expanded rats, and the administration of Hoe140 reduced PBF (-30%) and improved PBF autoregulation. The kinin antagonist also decreased sodium excretion (-35%) and blunted pressure natriuresis with no whole-kidney renal hemodynamic changes. These effects may be mediated through nitric oxide (NO), because in rats pretreated with N-G-nitro-L-arginine methyl ester, Hoe140 had no additional effects on PBF or pressure natriuresis, A role for NO in mediating the renal response to Hoe140 is also supported by the finding that Hoe140 reduced basal urinary NO3-/NO2- excretion (-33%), and it blunted the arterial pressure-induced increase in NO3-/NO2- excretion, which is compatible with the idea that the pressure-natriuresis response may be mediated through kinins and NO. The importance of kinins in long-term regulation of arterial pressure is demonstrated by the severe arterial hypertension (172+/-6 mm Hg) induced during the chronic intrarenal infusion of Hoe140 associated with sodium and volume retention. These data suggest that renal kinins and NO may be a part of the renal mechanism coupling changes in arterial pressure with modifications in PBF and sodium excretion, therefore contributing to the long-term control of arterial pressure.