Differential regulation of renal regional blood flow by endothelin-1

Abstract

The present study evaluated the effects and mechanisms of action of endothelin-1 (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively). CBF and MBF were measured simultaneously by laser-Doppler flowmetry in anesthetized male Wistar rats. Bolus injection of ET-1 (1.0 nmol/kg iv) produced a sustained decrease in CBF (delta = -30%) and a transient increase in MBF (delta = +35%). The medullary vasodilation induced by ET-1 was observed with doses lower than that required to produce cortical vasoconstriction; was completely blocked by bosentan, a mixed ETA/B-receptor antagonist; and was mimicked by IRL-1620, a specific ETB-receptor agonist. In contrast, BQ-123, an ETA-receptor antagonist, failed to inhibit the ET-1-dependent medullary vasodilation but effectively blocked the cortical vasoconstriction induced by the peptide. Finally, inhibition of nitric oxide (NO) synthase completely abolished, whereas cylooxygenase inhibition attenuated, the effect of ET-1 on MBF. The data demonstrate that ET-1 exerts opposite effects on renal cortical and medullary circulation, i.e., ETA-receptor-mediated cortical vasoconstriction and ETB-mediated medullary vasodilation. Furthermore, the medullary vasodilation induced by ET-1 is dependent on the NO system and, to a lesser extent, on prostaglandin generation.

Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems

“…To the best of our knowledge, the present study is the first one that examines whether selective ET A or ET B blockade can alter the changes in kidney function and renal hemodynamics caused by pneumoperitoneum. In line with its physiological vasodilatory action (14,19,25), blockade of ET B receptor aggravated the fall in GFR and RPF during pneumoperitoneum. This observation is further supported by our laboratory's previous findings that ET B receptor is preferably expressed in the outer and inner medulla, mainly in the vasa recta, thick ascending limb of Henles' loop, and collecting duct (11).…”

“…In this regard, several studies have demonstrated that medullary NO plays a pivotal role in the regulation of renal medullary hemodynamics and excretory function (27,28,30). Previously, our laboratory (14,18) and others (48) have shown that the renal vasodilatory actions of ET B , as well as its stimulatory effects on water and sodium excretion, are mediated through generation of NO. Similarly, Mattson et al (32) have demonstrated that chronic intravenous administration of the NO synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood flow, causes sodium and water retention, and leads to hypertension.…”

Peroxisome Proliferator-Activated Receptor-α Activation Reduces Salt-Dependent Hypertension During Chronic Endothelin B Receptor Blockade

“…There is an abundance of ET B receptors located in the renal medulla that promote sodium and water excretion by increasing medullary blood flow or through direct inhibition of tubular transport. 34,35 Other studies have observed that ET increases production of prostaglandin E 2 (PGE 2 ) in several cell types within the renal medulla. 36 -38 Furthermore, blockade of PGE 2 leads to a potentiation of ET-1-induced vasoconstriction.…”

Renal Parenchymal Hypoxia, Hypoxia Adaptation, and the Pathogenesis of Radiocontrast Nephropathy

“…Other prominent mediators that are believed to participate in the renal hemodynamic response to dye are adenosine (13,28), prostaglandins (29), and vasopressin (30). Indeed, the renal hemodynamic pattern of cortical vasoconstriction, coupled with preserved or even augmented medullary blood flow, resembles the renal microvascular response to the administration of some of these mediators, such as adenosine, endothelin, or angiotensin II (31)(32)(33). The disparate distribution of receptor subtypes of these mediators in the renal cortex and medulla may be responsible for the different regional hemodynamic responses.…”

“…Probably, for similar reasons, the use of nonselective endothelin receptor blockers has failed and, in fact, was found to affect adversely the clinical outcome (60). In the perspective of the important role of endothelin ET-B receptors in maintaining medullary blood flow (32), the use of selective ET-A receptor antagonists seems more reasonable (61). Indeed, such treatment was reported to attenuate radiocontrast-induced medullary hypoxia (62) and renal dysfunction (63) in experimental settings.…”