Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat.

Article Details

Citation

Kramp R, Fourmanoir P, Caron N

Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat.

Am J Physiol Renal Physiol. 2001 Dec;281(6):F1132-40.

PubMed ID
11704565 [ View in PubMed
]
Abstract

Renal blood flow (RBF) autoregulatory efficiency may be enhanced during NO inhibition in the rat, as recently reported. Under these conditions, endothelin (ET) synthesis and release may be increased. Our purpose was therefore to determine the role of ET in RBF autoregulatory changes induced by NO inhibition. To address this point, ET(A/B) receptors were blocked in anesthetized rats with bosentan, or selectively with BQ-610 or BQ-788. NO synthesis was inhibited with N(G)-nitro-L-arginine methyl ester (L-NAME). Mean arterial pressure (MAP) was decreased after bosentan (-10 mmHg; P < 0.01) or increased after L-NAME (25 mmHg; P < 0.001). RBF measured with an electromagnetic flow probe was reduced by L-NAME (-50%) and by BQ-788 (-24%). The pressure limits of the autoregulatory plateau (P(A) approximately 100 mmHg) and of no RBF autoregulation (P(o) approximately 80 mmHg) were significantly lowered by 15 mmHg after L-NAME but were unchanged after bosentan, BQ-610, or BQ-788. During NO inhibition, autoregulatory resetting was completely hindered by bosentan (P(A) approximately 100 mmHg) and by ET(B) receptor blockade with BQ-788 (P(A) approximately 106 mmHg), but not by ET(A) receptor blockade with BQ-610 (P(A) approximately 85 mmHg). These results suggest that the involvement of ET in the RBF autoregulatory resetting occurs during NO inhibition, possibly by preferential activation of the ET(B) receptor. However, the relative contribution of ET receptor subtypes remains to be further specified.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
BosentanEndothelin-1 receptorProteinHumans
Yes
Antagonist
Details
SitaxentanEndothelin-1 receptorProteinHumans
Yes
Antagonist
Details