Endothelial modulation of the coronary vasculature in vessels perfused via mature collaterals.

Abstract

Previous in vivo studies have shown that vasopressin, which releases the endothelium-derived relaxing factor and constricts coronary smooth muscle, produces augmented constriction of coronary microvessels perfused by mature collaterals. We hypothesized that chronic perfusion through collaterals produces endothelial dysfunction in the recipient vasculature. Mature collaterals were stimulated in mongrel dogs by the ameroid constrictor technique. After 3-6 months, rings of conduit vessels (obtuse marginals) were studied in organ chambers, and coronary microvessels (100-220 ,um) were studied in a pressurized, no-flow state with a microvessel imaging apparatus. Eleven dogs were used as controls. Large vessels were preconstricted with prostaglandin F2. to 30-70% of the maximum potassium chloride tension, and microvessels were preconstricted to 20-60% of the baseline diameter with the thromboxane mimetic U46619. Relaxations to the receptor-mediated agents acetylcholine and ADP were markedly impaired in collateral-dependent coronary microvessels, whereas relaxations to nitroglycerin were enhanced compared with microvessels from control dogs. Relaxation to the calcium ionophore A23187, which releases the endothelium-derived relaxing factor through nonreceptor-mediated mechanisms, were similar in control and ameroid microvessels. Constriction to vasopressin was augmented in collateral-dependent microvessels compared with controls. Responses to all agonists were similar between control and collateral-dependent large vascular rings. In conclusion, chronic perfusion through collateral vessels selectively impairs receptor-mediated endothelium-dependent relaxations and augments constriction to vasopressin in the coronary microcirculation. These findings may have important implications regarding neurohumoral regulation of perfusion to collateral-dependent myocardium. (Circulation 1990;81:1938-1947 A fter occlusion of a major coronary artery, the only blood flow to the ischemic myocardium arrives via coronary collaterals.

Endothelium-Mediated Relaxation of Porcine Collateral-Dependent Arterioles Is Improved by Exercise Training

“…C, RT-PCR experiments performed with freshly dispersed LAD and LCx endothelial cells similarly indicated that endothelium-specific GAPDH mRNA expression was unaltered by chronic coronary artery occlusion. responses to nitroprusside were not altered in coronary arterioles isolated from collateral-dependent myocardium of coronaryoccluded hearts, however, contradicts the previous findings of Sellke et al 12,13 of enhanced relaxation to sodium nitroprusside and nitroglyceride after chronic occlusion. The reasons for these differences are unclear but may relate to temporal differences between occlusion models, because Sellke et al evaluated endothelium-dependent relaxation in arterioles isolated 4 to 7 weeks after occlusion, whereas our arterioles were isolated 6 months after ameroid occlusion.…”

“…Because arteriolar smooth muscle responses to NO (nitroprusside) were unaffected, these findings indicate impairment of endothelium-dependent relaxation after chronic coronary artery occlusion, supporting similar results in previous publications. 12,13 Muller et al 8 and Parker et al 7 reported that coronary resistance arteries and arterioles isolated from normal female Yucatan swine exhibited enhanced bradykinin-mediated relaxation after exercise training. These findings stimulated our hypothesis that exercise training would improve impaired relaxation to bradykinin in collateral-dependent microvessels.…”

“…10,11 Conversely, canine and porcine hearts exposed to chronic coronary occlusion exhibit impaired endothelium-dependent vasorelaxation [12][13][14] and enhancement of selected vasoconstrictor responses. [12][13][14][15] Combined effects of coronary disease and exercise training on endothelial function are less clearly understood. In the present study, we evaluated exercise training-induced alterations of coronary endothelial function and ecNOS mRNA in porcine arterioles isolated from hearts exposed to chronic ameroid occlusion of the left circumflex coronary artery (LCx).…”

Exercise Training Enhances Vasodilation Responses to Vascular Endothelial Growth Factor in Porcine Coronary Arterioles Exposed to Chronic Coronary Occlusion

“…6 Furthermore, a significant body of evidence indicates that impaired endothelial function and altered vasomotor responsiveness of collateral-dependent vasculature contribute to abnormal regulation of coronary tone distal to CCO. [7][8][9][10] For instance, impaired endothelium-dependent nitric oxide (NO)-mediated vasodilation persists in the microvasculature distal to the occlusion 7,8,10 and is associated with CCO-induced reduction in endothelial cell NO synthase (ecNOS) mRNA in coronary arterioles. 10 Because NO plays pivotal roles in key endothelial signaling pathways, altered NO-dependent functions may have important consequences on vasomotor and angiogenic responses in the diseased heart.…”

Endothelium-Dependent Relaxation of Collateral Microvessels After Intramuscular Gene Transfer of Vascular Endothelial Growth Factor in a Rat Model of Hindlimb Ischemia

“…1 In vitro studies also have shown that endothelium-dependent relaxation of coronary collaterals is depressed markedly at the microvascular level. 2 Recent investigations have established that exogenously administered angiogenic growth factors can induce the formation of new blood vessels and enhance collateral blood flow to ischemic tissues. 3 A number of naturally occurring growth factors could potentially induce or accelerate angiogenesis by stimulating endothelial cell proliferation and migration.…”