(Circulation. 1995;92:518-525.)
© 1995 American Heart Association, Inc.
Articles |
Longitudinal Gradients for Endothelium-Dependent and -Independent Vascular Responses in the Coronary Microcirculation
From the Department of Medical Physiology, Microcirculation Research Institute, Texas A&M University Health Science Center, College Station.
Correspondence to Dr Lih Kuo, Department of Medical Physiology, Microcirculation Research Institute, Texas A&M University Health Science Center, College Station, TX 77843-1114.
Background Coronary microvessels (<300 µm in diameter) have been demonstrated to be important in the regulation of local resistance and flow. Recent studies also suggest that these microvessels are more responsive to physiological and pharmacological stimuli than conduit vessels. However, little is known regarding the relative sensitivity of different microvascular segments in response to flow (shear stress) and agonists. The goal of this study was to test the hypothesis that a longitudinal gradient for shear stress– and agonist-induced dilation exists in the coronary microcirculation.
Methods and Results Experiments were performed in four different
sizes of porcine subepicardial coronary arterial microvessels: small
arterioles (40±1-µm ID with resting tone); intermediate arterioles
(60±1 µm); large arterioles (106±4 µm); and small
arteries
(179±9 µm). Vessels were isolated and cannulated to allow luminal
pressure and flow to be independently controlled. All vessels developed
active tone (to 
65% to 75% of maximum diameter) at their control
luminal pressures and showed graded dilations to stepwise increases in
shear stress (0 to 10 dynes/cm2). For arterioles, the
magnitude of the dilations increased as vessel size increased. The
highest shear stress produced 21±3%, 32±2%, and 52±5%
increases
in diameter in small, intermediate, and large arterioles, respectively.
Small arteries dilated only 22±6%. The
endothelium-dependent vasodilator substance P (SP)
produced dose-dependent dilation of all vessels with a threshold at
10-16 mol/L. Arterioles were maximally dilated at
10-9 mol/L SP. However, this dose produced only 80%
dilation in small arteries. The ED50 for SP was shifted to
the right by two orders of magnitude in small arteries compared with
the arterioles. Adenosine preferentially dilated small arterioles, and
the dose-response curves shifted to the right for larger vessels. The
thresholds for adenosine-induced dilation were
10-12, 10-11, and
10-9 mol/L for small, intermediate, and large arterioles,
respectively. The endothelium-independent vasodilator
nitroprusside produced identical dose-dependent dilations in all vessel
segments.
Conclusions The results indicate that the pig coronary circulation exhibits a heterogeneity in physiological and pharmacological responses along the microvascular network. Small arterioles are more sensitive to adenosine, but large arterioles are more responsive to shear-stress stimulation. We speculate that site-specific preferential responses may play a crucial role in coordinating overall vascular function in the coronary microvascular network.
Key Words: endothelium-derived factors • vessels • microcirculation • substance P • adenosine
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