Nd. Kim et al., alpha(2)-adrenoceptor antagonists evoke endothelium-dependent and -independent relaxations in the isolated rat aorta, J CARDIO PH, 34(1), 1999, pp. 148-152
Citations number
28
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
This study was designed to determine whether the alpha(2)-adrennceptor anta
gonists idazoxan, yohimbine, and rauwolscine cause endothelium-dependent an
d -independent responses in the rat aorta. Rings of rat aorta, with and wit
hout endothelium, were suspended for the measurement of isometric force in
modified Krebs-Ringer bicarbonate solution (37 degrees C; aerated with 95%
O-2 and 5% CO2). The alpha(2)-aadeenocettor antagonists, in the concentrati
on range of 10(-8)-10(-6) M, relaxed phenylephrine-contracted rings with, b
ut not those without endothelium. alpha(2)-Adrenoceptor antagonists (3 x 10
(-6) M for 1 min) increased the accumulation of cyclic guanosine monophosph
ate (cGMP) about twofold in the aortas with endothelium. The relaxation and
the increased cGMP induced by alpha(2)-antagonists were attenuated by meth
ylene blue (10(-6) M) and N-G-nitro-L-arginine (L-NA, 3 x 10(-5) M), wherea
s propranolol (10(-6) M) did not affect the relaxation. In concentrations >
10(-6) M, a, adrenoceptor antagonists relaxed the rat aorta without endothe
lium. The endothelium-independent relaxation by andrenoceptor antagonists w
as abolished by increased external K+ and reduced significantly by tetraeth
ylammonium (TEA, 10(-2) M, a Ca2+-dependent K+ channel blocker), but not in
hibited by glibenclamide (10(-5) M, an ATP-scnsitive K+ channel blocker). I
n the rabbit aorta, only endothelium-independent relaxations were observed
with alpha(2)-andrenoceptor antagonists in the concentration range of 10(-8
)-10(-5) M, and these relaxations were not antagonized by TEA. These result
s suggest that alpha(2)-adrenoceptor antagonists relax the rat aorta throug
h endothelium-dependent mechanism at lower concentrations and endothelium-i
ndependent mechanisms at higher concentrations. The endothelium-dependent r
elaxations are likely to be mediated by the endothelium-derived relaxing fa
ctor (EDRF)/NO pathway because they are associated with the accumulation of
cGMP, whereas the endothelium-independent relaxations map be caused by the
opening of potassium channels in the vascular smooth muscle.