Published online before print November 13, 2003, doi: 10.1161/01.RES.0000106135.02935.E1
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© 2003 American Heart Association, Inc.
Integrative Physiology |
Rapid Inhibition of Vasoconstriction in Renal Afferent Arterioles by Aldosterone
From the Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark.
Correspondence to Ole Skøtt, Physiology and Pharmacology, University of Southern Denmark, DK-5000 Odense, Denmark. E-mail oskott{at}health.sdu.dk
Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10-10 to 10-5 mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes and was fully reversible. Actinomycin D (10-6 mol/L) prolonged the effect of aldosterone. The effect was abolished by the mineralocorticoid receptor antagonist spironolactone (10-7 mol/L) but not by the glucocorticoid receptor antagonist mifepristone (10-6 mol/L). The K+-mediated increase of intracellular calcium concentration in afferent arterioles was not affected by aldosterone. Mineralocorticoid receptor was detected by reverse transcription–polymerase chain reaction and immunohistochemistry in rat renal vasculature and rabbit endothelial cells. Inhibition of phosphatidylinositol (PI)-3 kinase with LY 294002 (3x10-6 mol/L) restored sensitivity to K+ in the presence of aldosterone, and afferent arterioles were immunopositive for PI-3 kinase subunit p110
. Inhibition of NO formation by L-NAME (10-4 mol/L) or inhibition of soluble guanylyl cyclase with 1H-(1,2,4)Oxadiazolo[4,3-a]quinoxaline-1-one restored K+-induced vasoreactivity in the presence of aldosterone. Similar to aldosterone, the NO donor sodium nitroprusside inhibited K+-induced vascular contraction. Geldanamycin (10-6 mol/L), an inhibitor of heat shock protein 90, abolished aldosterone-induced vasorelaxation. We conclude that aldosterone inhibits depolarization-induced vasoconstriction in renal afferent arterioles by a rapid nongenomic mechanism that is initiated by mineralocorticoid receptor activation and involves PI-3 kinase, protein kinase B, and heat shock protein 90–mediated stimulation of NO generation.
Key Words: endothelium • steroid • kidney • smooth muscle
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