Direct measurements of endothelium-derived nitric oxide release by stimulation of endothelin receptors in rat kidney and its alteration in salt-induced hypertension

Stimulation of endothelin subtype B (ETB) receptors has been proposed to induce release of endothelium-derived nitric oxide (EDNO). To obtain direct evidence of its release and its alteration in deoxycorticosterone acetate (DOCA)-salt hypertension, EDNO released from renal vessels by ET stimulation...

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Veröffentlicht in:Circulation (New York, N.Y.) N.Y.), 1995-02, Vol.91 (4), p.1229-1235
Hauptverfasser: HIRATA, Y, HAYAKAWA, H, SUZUKI, E, KIMURA, K, KIKUCHI, K, NAGANO, T, HIROBE, M, OMATA, M
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Sprache:eng
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Zusammenfassung:Stimulation of endothelin subtype B (ETB) receptors has been proposed to induce release of endothelium-derived nitric oxide (EDNO). To obtain direct evidence of its release and its alteration in deoxycorticosterone acetate (DOCA)-salt hypertension, EDNO released from renal vessels by ET stimulation was assayed by a highly sensitive chemiluminescence method. Kidneys were isolated from DOCA-salt and control rats, and renal perfusion pressure (RPP) and EDNO (by hydrogen peroxide-luminol chemiluminescence) in the perfusate were monitored simultaneously during perfusion of ET-1, ET-3, an ETA receptor antagonist (BQ-123), and an ETB receptor agonist (BQ-3020). In control rats, ET-1 and ET-3 dose-dependently increased both RPP and NO release. Although the vasoconstricting effects of ET-1 were greater, their NO-releasing effects were comparable. The increase in NO release by ETs was inhibited by NG-monomethyl-L-arginine. After 10(-6) mol/L BQ-123 treatment, ET-1 decreased RPP and increased NO release in control kidneys. DOCA-salt rats responded to these agents with much less NO release. BQ-3020 at up to 10(-10) mol/L caused vasodilation (RPP, 10(-11) mol/L, -5.4 +/- 1.7%, P < .01) associated with increased NO release in control kidneys (+9.0 +/- 2.7 fmol.min-1.g-1 kidney wt, P < .01). However, in DOCA-salt kidneys, BQ-3020 caused renal vasoconstriction (RPP, +5.4 +/- 2.4%, P < .01 versus control) and a much smaller NO release (+1.1 +/- 0.4 fmol.min-1.g-1 kidney wt, P < .01 versus control). Northern blot analysis revealed that renal ETB mRNA was significantly decreased in DOCA-salt rat kidneys compared with controls (0.36 +/- 0.13 versus 1.00 +/- 0.23, P < .05). These results suggest that ET-1 and ET-3 release EDNO via ETB receptors in renal vessels. ETB-mediated NO release was reduced in DOCA-salt rats, which may modulate renal function and thus blood pressure regulation in DOCA-salt hypertensive rats.
ISSN:0009-7322
1524-4539
DOI:10.1161/01.cir.91.4.1229