Circulation, Vol 87, 1264-1274, Copyright © 1993 by American Heart Association
CJ Jones, DV DeFily, JL Patterson and WM Chilian
BACKGROUND. The purpose of this study was to determine whether
endothelium-dependent relaxation competes with alpha 1- and alpha 2-
adrenergic coronary microvascular constriction in the beating heart in
vivo. METHODS AND RESULTS. Coronary microvascular diameters were measured
using stroboscopic epi-illumination and intravital microscopy during
fluorescein microangiography in open-chested dogs (n = 20). Both alpha 1-
and alpha 2-adrenergic receptors were selectively activated by
intracoronary infusions of norepinephrine (0.05 and 0.2 microgram.kg-1 x
min-1) in the presence of the alpha 2-adrenergic antagonist rauwolscine
(0.2 mg/kg) or the alpha 1-adrenergic antagonist prazosin (0.75 mg/kg)
during beta-adrenergic blockade (1 mg/kg propranolol). Microvascular
diameters during selective alpha-adrenergic receptor activation were
measured under baseline conditions and after inhibition of endogenous
nitric oxide synthesis by an analogue of L-arginine, either
NG-nitro-L-arginine (L-NA, 30 mg/kg) or NG-nitro-L-arginine methyl ester
(L-NAME, 30 mg/kg). Under baseline conditions, alpha 1- adrenergic
activation constricted small arteries (vessels with diameters between 100
and 300 microns) (4 +/- 1% and 5 +/- 1% decrease in diameter for the low
and high doses of norepinephrine, respectively, both p < 0.05) but did
not change the diameter of arterioles (vessels with diameters < 100
microns). In contrast, alpha 2-adrenergic activation by the lower but not
the higher dose of norepinephrine induced constriction of arterioles (6 +/-
2% and 3 +/- 4% decrease in diameter, p < 0.05 and NS, respectively) but
not small arteries. Inhibition of nitric oxide synthase activity by either
L-NA or L-NAME produced constriction of small coronary arteries (9 +/- 2%
decrease in diameter, p < 0.01) and arterioles (6 +/- 1% decrease in
diameter, p < 0.05). The dilatation of small arteries and arterioles by
acetylcholine (0.05 microgram-1 x kg-1 x min-1 intracoronary infusion; 10
+/- 1% increase in diameter under baseline conditions, p < 0.05) was
abolished by either analogue. Both alpha 1- and alpha 2-adrenergic coronary
microvascular constriction were markedly potentiated after L-NA or L- NAME.
alpha 1-Adrenergic constriction was unmasked in arterioles (7 +/- 3% and 10
+/- 4% decrease in diameter, p < 0.05), although it was not
significantly increased in small arteries. Conversely, alpha 2- adrenergic
constriction was unmasked in small arteries (8 +/- 1% and 6 +/- 2% decrease
in diameter, both p < 0.05) and potentiated in arterioles (12 +/- 1% and
8 +/- 4% decrease in diameter, both p < 0.05). After L-NA or L-NAME,
microvessels retained the ability to dilate to sodium nitroprusside (0.1
microgram.kg-1 x min-1 intracoronary infusion; 10 +/- 2% increase in
diameter, p < 0.05). alpha-Adrenergic constriction was not accentuated
by increased tone alone, since it was either attenuated or converted to
dilatation during a similar degree of preconstriction by the
endothelium-independent vasoconstrictor angiotensin II (p < 0.05 for
both alpha 1- and alpha 2- adrenergic activation). CONCLUSIONS. These data
confirm that alpha- adrenergic receptors are widespread in the coronary
microcirculation, with the baseline functional responses to alpha
1-adrenergic activation predominating in small arteries and those to alpha
2-adrenergic activation predominating in arterioles. Furthermore, coronary
microvascular constriction caused by both alpha 1- and alpha 2- adrenergic
receptor activation is significantly modulated by endothelium-dependent
relaxation, being markedly potentiated by inhibition of nitric oxide
synthase activity. The data imply that alpha- adrenergic activation will
assume considerable importance as a determinant of coronary microvascular
resistance in pathophysiological situations associated with coronary
endothelial impairment.
ARTICLES
Endothelium-dependent relaxation competes with alpha 1- and alpha 2- adrenergic constriction in the canine epicardial coronary microcirculation
Department of Medical Physiology, Texas A&M University Health Science Center, College Station 77843-1114.
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