Glomerular actions of endothelin in vivo.

Abstract

In Munich-Wistar rats, a micropipette was inserted into a first-order branch of the left main renal artery and continuously infused with human/porcine endothelin (0.4 ng/min). Micropuncture measurements revealed substantial differences within the cortical microcirculation of the same left kidney: SNGFR was some 35% lower in glomeruli exposed to endothelin compared with non-endothelin-perfused glomeruli (P < 0.005). Similarly, glomerular plasma flow rate was some 38% lower in the endothelin-exposed glomeruli (P < 0.001). The hypoperfusion and hypofiltration in the endothelin-exposed glomeruli reflected an increase in resistances in the afferent and efferent arterioles. There was no difference in the value of the glomerular capillary ultrafiltration coefficient between the two populations of glomeruli.We also studied kidneys that underwent 25 min of renal artery clamping 48 h before study. Antiendothelin antibody infused into one of the branches of the main renal artery ameliorated the vasoconstriction characteristic of postischemic nephrons: within the cortical microcirculation, the SNGFR in glomeruli exposed to antiendothelin antibody was 27.0±3.1 nl/min as compared with 17.4±1.7 measured in glomeruli not perfused with the antibody (P < 0.001). Similarly, glomerular plasma flow rate was higher in the glomeruli exposed to antiendothelin antibody (128.7±14.4 nl/min vs. 66.6±5.6, P < 0.005). Resistances in both the afferent and efferent arterioles were substantially lower in the antibody-exposed glomeruli. It is, therefore, suggested that endothelin, presumably released from damaged endothelium, may play an important intermediary role in the hypoperfusion and hypofiltration observed in postischemic kidneys. Introduction Vasomotor tone is controlled by dynamic interplay of neurogenic and myogenic mechanisms and circulating hormones. In the last several years, evidence has accumulated that the endothelium elaborates both vasoconstrictive and vasodilative substances, thereby participating in this dynamic regulation of vascular tone MethodsAll experiments were done in male Munich-Wistar rats weighing 180-230 g. The animals were allowed access to standard rat chow and tap water until the day ofthe experiment. Group 1 animals consisted of seven normal rats. The animals were prepared for micropuncture as previously described (4-6). Briefly, under anesthesia (70 mg Inactin/kg body wt i.p.; BYK, FRG) tracheostomy was performed and indwelling polyethylene catheters were inserted into the femoral artery and vein and jugular vein for blood sampling, monitoring of systemic blood pressure, infusion of plasma, and inulin as previously described (4-6). In addition, one ofthe main branches ofthe left main artery was gently isolated. Care was taken not to disrupt the renal nerves and lymphatics. This branch vessel was momentarily (< 5 s) occluded with fine forceps and distribution of its blood flow was marked on the surface of the kidney with a permanent ink marker by noting the blanching of the kidney surface. Using micro...

Endothelin stimulated by angiotensin II augments contractility of spontaneously hypertensive rat resistance arteries.

“…A 1:20,000 dilution of antiserum binds approximately 50% of radiolabeled endothelin at a concentration of 1.0 pmol/ml. The antiserum was diluted 1:100 with phosphate buffer solution (pH 7.40) and was infused intraluminally 25 through the polyethylene catheter in the afferent cannula, which was connected to a syringe on a microinfusion pump (model 22, Harvard Apparatus, South Natick, Mass.). For the intraluminal application of the antiserum, flow rate through the vascular segment was measured repeatedly at the efferent cannula (since flow changes with changes in vascular diameter), and infusion rate of intraluminally applied drug was adjusted accordingly to assure a constant concentration of the drug in perfusate.…”

Epidermal growth factor (EGF) decreased endothelin‐2 (ET‐2) production in human renal adenocarcinoma cells

“…ET-I showed various pharmacological activities in both cardiovascular and non-cardiovascular tissues [3]. Especially, ET-I is thought to play important roles in the kidney in the control of mesangial cell function, glomerular filtration rate, renal vascular tone [4] and ion transport/water permeability [5].…”

Endothelins: a family of regulatory peptides. State-of-the-art lecture.

“…39 Because hypoxia is a potent stimulus of ET release, Firth et al 40 suggested that ET mediates hemodynamically induced acute renal failure. Support for this view comes from the work of Kon and coworkers, 41 who showed in a model of postischemic renal injury that ET-neutralizing antibodies reverse the reduction in single nephron glomerular filtration rate and renal blood flow. Thus, ET released by damaged endothelium or mesangial cells might contribute to the hypoperfusion and hypofiltration seen in postischemic renal injury.…”