SELECTIVE LARGE CORONARY ENDOTHELIAL DYSFUNCTION IN CONSCIOUS DOGS WITH CHRONIC CORONARY PRESSURE-OVERLOAD

Coronary vascular responses to acetylcholine (ACh, 3 mu g/kg iv), nitr oglycerin (NTG, 25 mu g/kg iv), and a 20-s coronary artery occlusion ( reactive hyperemia, RH) were investigated in seven conscious dogs with severe left ventricular (LV) hypertrophy and chronic coronary pressur e overload (CCPO) due to supravalvular aortic banding and in seven con trol dogs. All dogs were instrumented for measurement of ultrasonic co ronary diameter (CD) and Doppler coronary blood flow (CBF). LV-to-body weight ratio was increased by 82% in CCPO dogs. In control dogs, ACh increased CD (+5.9 +/- 1.7%). This response was reduced (P < 0.05) in CCPO dogs (+1.9 +/- 0.9%). Similarly, flow-mediated increases in CD af ter RH were blunted (P < 0.01) in CCPO (+2.1 +/- 0.8) vs. control dogs (+6.8 +/- 1.8%). In contrast, ACh and RH increased CBF similarly in b oth groups. Increases in both CD and CBF to NTG were not different bet ween control dogs and CCPO. Peak systolic CBF velocity was greater, P < 0.01, in CCPO (94 +/- 17 cm/s) compared with control (35 +/- 7 cm/s) dogs, most likely secondary to the increased systolic coronary perfus ion pressure (215 vs. 130 mmHg). Histological analyses of large corona ry arteries in CCPO revealed medial thickening, intimal thickening, an d disruption of the internal elastic lamina and endothelium. In contra st, small intramyocardial arterioles failed to show the intimal and en dothelial lesions. Thus. in CCPO selective to the coronary arteries, i .e., a model independent from systemic hypertension and enhanced level s of plasma renin activity, endothelial control was impaired for both flow-mediated and receptor-mediated large coronary artery function, wh ich could be accounted for by the major morphological changes in the l arge coronary arteries sparing the resistance vessels. The mechanism m ay involve chronically elevated systolic coronary perfusion pressure, CBF velocity, and potential disruption of laminar flow patterns.