Beta-adrenergic modulation of the collateral-dependent coronary microcirculation.
The effect of chronic, collateral-dependent perfusion on beta-adrenergic coronary microvascular responses was examined. Ameroid constrictors were placed on the proximal left circumflex (LCx) coronary artery in 16 pigs. In 8 pigs, heparinized saline containing vascular endothelial growth factor (VEGF) was administered into the perivascular space of the proximal LCx artery using an implanted osmotic pump. After 5-7 weeks, coronary arterial microvessels (70-150 microns) were studied in a pressurized (40 mm Hg) no-flow state with video-microscopy. beta-Adrenoceptor-mediated relaxations of isolated microvessels from the collateral-dependent LCx region to isoproterenol (P < 0.01) were markedly reduced, as were those to the adenylate cyclase activator forskolin (P < 0.01), compared to the respective response of vessels from the normally perfused left anterior descending artery region. Responses to the Gs-protein activator NaF showed a similar trend, but the differences were not significant. Chronic treatment with VEGF normalized responses to isoproterenol, NaF, and forskolin in the collateral-dependent LCx region. Blood flow in the LCx region increased in both control (P < 0.01) and VEGF-treated (P < 0.05) groups during rapid atrial pacing. The absolute increase in LCx blood flow was greater in the VEGF group than in the control group at rest (P < 0.05), but not during rapid pacing. Thus, beta-adrenergic microvascular relaxation is impaired in the collateral-dependent coronary microcirculation. The periadventitial delivery of VEGF improves myocardial perfusion to the collateral-dependent area and preserves beta-adrenergic-mediated relaxation of microvessels in the collateral-dependent myocardium.
Sellke
F W
FW
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
Wang
S Y
SY
Friedman
M
M
Dai
H B
HB
Harada
K
K
Lopez
J J
JJ
Simons
M
M
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology; D016228:Endothelial Growth Factors / Q000494:pharmacology; D005260:Female; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010477:Perfusion; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013552:Swine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014664:Vasodilation / Q000187:drug effects
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011943:Receptors, Adrenergic, beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000242:Cyclic AMP