Differential action of bradykininon intrarenal regional perfusion in the rat: waning effect in the cortex and major impact in the medulla

摘要

The renal kallikrein-kinin system is involved in the control of the intrarenal circulation and arterial pressure but bradykinin (Bk) effects on perfusion of individual kidney zones have not been examined in detail. Effects of Bk infused into renal artery, renal cortex or medulla on perfusion of whole kidney (RBF, renal artery probe) and of the cortex, outer- and inner medulla (CBF, OMBF, IMBF: laser-Doppler fluxes), were examined in anaesthetized rats. Renal artery infusion of Bk, 0.3-0.6 mg kg~(-1) h~(-1), induced no sustained increase in RBF or CBF. OMBF and IMBF increased initially 6 or 16%, respectively; only the IMBF increase (+10%) was sustained. Pre-treatment with l-NAME, 2.4 mg kg~(-1) I.V., prevented the sustained but not initial transient elevation of medullary perfusion. Intracortical Bk infusion, 0.75-1.5 mg kg~(-1) h~(-1), did not alter RBF or CBF but caused a sustained 33% increase in IMBF. Intramedullary Bk, 0.3 mg kg~(-1) h~(-1), did not alter RBF or CBF but caused sustained increases in OMBF (+10%) and IMBF (+23%). These responses were not altered by pre-treatment with 1-aminobenzotriazole, 10 mg kg~(-1) I.V., a cytochrome P-450 (CYP450) inhibitor, but were prevented or significantly attenuated by l-NAME or intramedullary clotrimazole, 3.9 mgkg~(-1) h~(-1), an inhibitor of CYP450 epoxygenase and of calcium-dependent K~+ channels (K_ca)- Thus, cortical vasodilatation induced by Bk is only transient so that the agent is unlikely to control perfusion of the cortex. Bk selectively increases perfusion of the medulla, especially of its inner layer, via activation of the NO system and of K_Ca channels.