Effects of Endothelin on the Renal Microcirculation of the Split Hydronephrotic Rat Kidney

Abstract

We have examined the effects of endothelin (ET) on the renal microcirculation by in vivo microscopy using the model of the split hydronephrotic rat kidney. ET, a potent vasoconstrictor peptide synthesized by vascular endothehal cells, showed marked and long-lasting effects on glomerular blood flow and vessel diameters in various segments of the renal vascular bed. Intravenously applied ET (100 ng/min/kg) increased systemic blood pressure from 123 ± 7 to 156 ± 4 mm Hg, decreased glomerular blood flow by 70%, and preferentially constricted larger preglomerular vessels, e.g. the arcuate artery. The competitive leukotriene antagonist FPL55712 significantly attenuated the vascoconstrictor response of the larger vessels. Local ET adminstration decreased glomerular blood flow in a dose-dependent manner (50% reduction at a concentration of 2.6 ± 0.7 · 10^-9M) and constricted smaller vessel segments, e.g. the afferent and efferent arterioles near the glomerulus. The constriction induced by ET was not significantly affected by the Ca²⁺ channel blocker nitrendipine (2.8 · 10^-6 to 1.1 · 10^-5M). We conclude that intravenous ET effects are probably mediated by leukotrienes, inducing constriction of larger renal vessels. Locally administered ET acts directly on the renal vasculature, especially on smaller vessels.

Relative roles of nitric oxide and cyclo‐oxygenase and lipoxygenase products of arachidonic acid in the contractile responses of rat renal arcuate arteries

“…This finding is contrary to the data of Fretschner et al (1991) who examined the effect of endothelin-l in the split hydronephrotic kidney model. They demonstrated that the response to endothelin-1 was attenuated by a competitive leukotriene antagonist.…”

Prostaglandin E2 abrogates endothelin-induced vasoconstriction in renal outer medullary descending vasa recta of the rat.

“…Edwards et al showed that rabbit efferent and afferent arterioles constrict in response to ET-1 and ET-2 (ECm -1 nM) while ET-3 is significantly less potent (35). Similarly, in the hydronephrotic rat kidney both efferent and afferent arterioles constricted in response to topical or lumenal administration of ETs, however, the afferent arteriole may be more sensitive (36)(37)(38). Other investigators have demonstrated the ability of ET to alter glomerular filtration rate and renal vascular resistance in vivo (1).…”

Visualization of Renal Microcirculation in Isolated Munich-Wistar Rat Kidneys: Effects of Endothelin-1 on Renal Hemodynamic Activity

“…For example, Loutzenhiser et al (27) reported that, in the isolated perfused hydronephrotic kidney, ET-1 was a po tent vasoconstrictor of the afferent arterioles with a threshold vasoconstriction response at a dose of 0.01 nM, whereas it had a lesser effect in reducing the efferent arteriolar diameter. Fretschner et al (28) used a split hydronephrotic rat kidney model and found that in travenous ET-1 (100 ng/kg/min) induced elevated sys temic blood pressure, decreased glomerular blood flow and preferentially constricted larger preglomerular vessels such as the arcuate artery. However, to our knowledge, no direct demonstration of the involvement of the affer ent or efferent arterioles in normal kidneys has been made to date; the studies cited above were carried out in special ized kidneys, such as the hydronephrotic kidney.…”