Endothelin receptor a blockade alters the hemodynamic response to
nitric oxide inhibition in the rat.
Thompson, Alex, C. Robert Valeri, and Wilfred Lieberthal.
Renal Section, Evans Memorial Department of Clinical Research and
Department of Medicine, and the Naval Blood Research Laboratory,
Boston University Medical Center, MA 02118
APStracts 2:0228H, 1995.
We have examined the extent to which the systemic and renal
vasoconstriction induced by nitric oxide (NO) inhibition in vivo are
mediated by endothelin (ET). We examined the effects of BQ610, a
specific ET-A receptor antagonist, following NO inhibition with L
-NAME in the anesthetized rat. Mean arterial pressure (MAP) increased
following L-NAME infusion from 107+/-2 to 133+/-3 mmHg (p<0.05
vs baseline period) and then fell to 115+/-3mmHg following
administration of BQ610 (p<0.05 vs L-NAME and baseline periods).
Systemic vascular resistance (SVR) increased from 1.26+/-0.06 to
2.17+/-0.18 mmHg/ml/min/300g following L-NAME (p<0.05 vs
baseline period) and then fell to 1.69+/-0.12 mmHg/ml/min/300g after
BQ610 (p<0.05 vs L-NAME and baseline periods). The increase in
renal vascular resistance (RVR) from 6.4+/-0.4 to 13.7+/-1.4
mmHg/ml/min/300g induced by L-NAME (p<0.05 vs baseline period)
was reduced to 11.1+/-1.0 mmHg/ml/min/300g by BQ610 (p<0.05 vs
L-NAME and baseline periods). The extent to which BQ610 reversed the
L-NAME induced increases in RVR and SVR was comparable (RVR by 40+/
-9% ; SVR by 52+/-7%). GFR and renal blood flow (RBF) were both
reduced by L-NAME, but neither value increased following BQ610,
possibly because the renal vasodilation induced by ET-A blockade was
offset by the concomitant reduction in MAP and renal perfusion
pressure. In summary, ET, acting via the ET-A receptor, partially
contributes to the systemic and renal hemodynamic vasoconstrictor and
hypertensive effects of NO inhibition.
Received 23 May 1995; accepted in final form 19 May 1995.
APS Manuscript Number H280-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 June 1995.