In vivo and in vitro vasoactive reactions of coronary arteriolar
microvessels to nitroglycerin.
Jones, Christopher J. H., Lih Kuo, Michael J. Davis, and William M.
Chilian.
University of Wales College of Medicine, Cardiff, UK and Department
of Medical Physiology, Microcirculation Research Institute, Texas
A&M University Health Science Center, College Station, Texas
APStracts 3:0020H, 1996.
The actions of nitroglycerin on the coronary microcirculation are
controversial with some laboratories reporting that coronary
arterioles dilate to the drug, whereas others report that they do
not. Our goal was to delineate the actions of nitroglycerin on the
coronary microcirculation to reconcile disparate observations in the
literature. Specifically, we hypothesized that dilation of coronary
arterioles less than 100 m in diameter by nitroglycerin is
overwhelmed by intrinsic autoregulatory escape mechanisms.
Accordingly, we projected that coronary arterioles would show
transient, but not sustained, dilation to nitroglycerin in vivo.
Furthermore, we hypothesized that isolated coronary arterioles would
show sustained dilation to the drug, because intrinsic escape
mechanisms related to alterations in intraluminal pressures or local
concentrations of metabolites would be absent under in vitro
conditions. To test these hypotheses, we measured diameter changes
during continuous nitroglycerin administration in canine coronary
microvessels in vivo using intravital microscopy during fluorescein
microangiography (n=17 dogs) at two points in time following
initiation of intracoronary infusion or epicardial suffusion: early
(1-3 minutes), when coronary artery blood flow velocity was increased
and late (15-20 minutes), after blood flow velocity had returned to
control. To study responses of coronary arterioles in the absence of
autoregulatory influences, we measured the diameter of isolated
canine coronary arterioles in vitro, during graded applications of
nitroglycerin at constant pressure (n=8 vessels, maximal diameter 81
4 m). Between 1 and 3 minutes after the onset of intracoronary
infusion of nitroglycerin in vivo (1, 3 and 10 g/kg[tilde]nmin)
coronary arterioles less than 100 m in diameter had dilated by 4 1%,
7 2% and 13 2% (all p<0.05), and small arteries greater than 100
m in diameter had dilated by 1 2%, 3 1% and 4 1% respectively
(p<0.05 for the higher doses). Upstream coronary artery blood
velocity measured by Doppler flowmetry had increased by 45 15% (3
g/kg[tilde]nmin, p<0.05). Also, nitroglycerin administration by
topical suffusion (10-5 M) dilated coronary arterioles by 17 5%
(p<0.05) between 1 and 3 minutes, but did not dilate small
arteries. After 15 to 20 minutes of nitroglycerin (3 g/kg[tilde]nmin
by intracoronary infusion) the diameters of coronary arterioles had
returned to control (3 2%, p<0.05 versus the earlier change),
whereas the dilation of small arteries remained significant at 4 1%,
and coronary artery blood velocity had returned to control values.
Coronary arteriolar dilation by epicardial suffusion of nitroglycerin
also waned to 3 2% (p<0.05 v. earlier change) by 15 to 20
minutes, whereas the dilation of small arteries became significant at
5 2% (p<0.05). In vitro, nitroglycerin (10-9 to 10-4 M) caused
dose-dependent dilation of coronary arterioles to their maximal
diameter, which was sustained for 20 minutes. Thus, nitroglycerin
dilates coronary arterioles and small arteries. The dilation in vivo
is transient for arterioles, but sustained for arteries. In vitro,
the dilation is sustained. Because the microvessels in vitro are
capable of sustaining dilation for 20 minutes, we conclude the waning
of arteriolar dilation in vivo is related to autoregulatory escape
from dilation by nitroglycerin.
Received 21 September 1995; accepted in final form 20 December
1995.
APS Manuscript Number H893-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96