Mechanisms of Adrenomedullin-Induced Vasodilation in the Rat Kidney

Abstract

To explore the mechanisms of adrenomedullin-induced vasorelaxation, we tested the effects of adrenomedullin on renal function in rats in vivo and measured the release of endothelium-derived nitric oxide from isolated perfused rat kidney (using a chemiluminescence assay) and the diameters of the glomerular arterioles in the hydronephrotic kidney. Adrenomedullin decreased blood pressure in a dose-dependent manner (3 nmol/kg: -29 +/- 2% [SEM]; P < .01) and slightly increased the glomerular filtration rate and urinary sodium excretion (+108%; P < .05). These changes were associated with significant increases in urinary excretion of cyclic AMP (+54%; P < .05). Adrenomedullin decreased renal vascular resistance (10(-7) mol/L adrenomedullin: -41 +/- 2%; P < .001) and increased release of nitric oxide (+5.1 +/- 0.7 fmol/min per gram kidney weight; P < .001) in the isolated kidney. This increase in nitric oxide release was abolished by the inhibitor NG-monomethyl-L-arginine, and it also reversed the decrease in renal vascular resistance seen with adrenomedullin. Renal responses of deoxycorticosterone acetate-salt hypertensive rats to adrenomedullin were significantly smaller than those of control rats for both release of nitric oxide (10(-7) mol/L adrenomedullin: +0.8 +/- 0.2 fmol/min per gram kidney weight; P < .01 versus control) and renal vasodilation (-28 +/- 6%; P < .05). Videomicroscopic analysis revealed that adrenomedullin increased the diameters of both afferent and efferent arterioles (3 nmol/kg: +11%; P < .05). Thus, adrenomedullin-induced renal vasodilation is partially endothelium dependent and is attenuated in deoxycorticosterone acetate-salt hypertension, probably due to endothelial damage.

Proadrenomedullin N-Terminal 20 Peptide (PAMP) Immunoreactivity in Vertebrate Juxtaglomerular Granular Cells Identified by Both Light and Electron Microscopy

“…In addition, Jensen et al (1996Jensen et al ( , 1997 have identified by RT-PCR the presence of AM in afferent and efferent arterioles, but not in juxtaglomerular granular cells in culture. They have also confirmed the stimulation of renin release by AM, an event previously reported by Hirata et al (1995).…”

Regional Hemodynamic Effects of Adrenomedullin in Wistar Rats: A Comparison with Calcitonin Gene-Related Peptide.

“…For example, AM dilates the renal vasculature, and the kidneys show one of the highest levels of expression and secretion of AM (25). AM exhibits diuretic and sodium-excreting effects associated with renal vascular dilation (26,27). On the other hand, in a study by Cheung et al, patients with chronic respiratory disorders and secondary pulmonary hypertension showed an elevation in plasma AM (28).…”

Adrenomedullin and Nitric Oxide Inhibit Human Endothelial Cell Apoptosis via a Cyclic GMP-Independent Mechanism

“…27 When adrenomedullin was added to the cultures together with 2 mmol/L L-NAME, an inhibitor of NO synthase, the antiapoptotic effect was completely abrogated (Figures 4A and 4B). Furthermore, SNP (10 mol/L), a NO donor, mimicked the antiapoptotic effect of adrenomedullin.…”