AJP - Renal Physiology, Vol 259, Issue 2 217-F221, Copyright © 1990 by American Physiological Society
Renal microvascular effects of endothelin
R. M. Edwards, W. Trizna and E. H. Ohlstein
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
The effects of endothelin 1, 2, and 3 (ET-1, -2, -3) on lumen diameter of
individual afferent and efferent arterioles dissected from rabbit kidney
were examined. ET-1 produced concentration-dependent and long-lasting
decreases in lumen diameter in both arterioles. The 50% maximum response
(EC50) values were 1.4 +/- 0.41 and 0.9 +/- 0.65 nM for afferent and
efferent arterioles, respectively. In afferent arterioles, ET-2 produced
decreases in lumen diameter (EC50 = 3.3 +/- 1.75 nM) that were
indistinguishable from ET-1. However, ET-3 was considerably less potent
(EC50 = 21.9 +/- 6.0 nM, P less than 0.05) than ET-1 or ET-2. Similar
results were obtained in the efferent arteriole in which the EC50 for ET-2
(0.25 +/- 0.1 nM) was similar to ET-1, but ET-3 was significantly less
potent (EC50 = 2.6 +/- 0.4 nM, P less than 0.05). Nicardipine (0.01-1
microM) produced concentration-dependent shifts in the ET-1
concentration-response curve in afferent arterioles. Verapamil (1 microM)
also caused a significant shift in the ET-1 response curve. The contractile
response to ET-1 was significantly more sensitive to nicardipine than was
the response to norepinephrine. In contrast, the response of efferent
arterioles to ET-1 and norepinephrine was unaffected by nicardipine or
verapamil. The results demonstrate that ETs are potent vasoconstrictors of
both the pre- and postglomerular microvasculature and may play a role in
the regulation of renal hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)
