Endothelin-1 (ET-1) is secreted from all rat vascular smooth muscle cells (
VSMCs) examined, in addition to endothelial cells (ECs). An average secreti
on rate of ET-1 from rat VSMCs was determined to be 10% that excreted from
ECs. We examined the effects of 22 substances on ET-1 secretion from VSMCs
and compared them with those from ECs. Transforming growth factor-beta (1)
(TGF-beta), acidic and basic fibroblast growth factors, epidermal growth fa
ctor, angiotensin II, and adrenaline stimulated ET-1 secretion from VSMCs,
whereas forskolin, thrombin, and platelet-derived growth factor-BE reduced
it. Only TGF-beta and phorbol ester elicited consistent effects on ET-1 sec
retion from VSMCs and ECs. Regulation of ET-1 and adrenomedullin secretion
from VSMCs was distinctly different. These data suggest that ET-1 productio
n in VSMCs is regulated by a mechanism separate from that in ECs and from a
drenomedullin production in VSMCs. Chromatographic analysis showed immunore
active ET-1 secreted from VSMCs was mainly composed of big ET-1. whereas ap
proximately 908 of that from ECs was ET-1. By TGF-beta stimulation of VSMCs
, the ratio of big ET-1 to ET-1 was further increased. Because big ET-1 is
converted into ET-1 only on the surface of the ECs in the culture system, b
ig ET-1 secreted from the VSMCs may function as a mediator transmitting a s
ignal from VSMCs to ECs in vivo.