Direct measurements of endothelium-derived nitric oxide release by stimulation of endothelin receptors in rat kidney and its alteration in salt-induced hypertension.
BACKGROUND
Stimulation of endothelin subtype B (ETB) receptors has been proposed to induce release of endothelium-derived nitric oxide (EDNO).


RESULTS
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).


CONCLUSIONS
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.
Second Department of Internal Medicine, University of Tokyo, Japan.
Y
Y
Hirata
H
H
Hayakawa
E
E
Suzuki
K
K
Kimura
K
K
Kikuchi
T
T
Nagano
M
M
Hirobe
M
M
Omata
D000818:Animals; D003900:Desoxycorticosterone; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism*; D008163:Luminescent Measurements; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology*; D012965:Sodium Chloride; D014655:Vascular Resistance / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C075771:BQ 3020; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C072247:cyclo(Trp-Asp-Pro-Val-Leu)