Of these agents, the key factors appear to be adenosine, NO, opening of the KATP channels, and H2O2. The contributions of each of these agents and their interaction under basal conditions and during increased myocardial •Fig. 17.33 RelationshipbetweenmyocardialO2consumptionandcoronarybloodflowduringavarietyofinterventionsthatincreaseordecreasethemyocardialmetabolicrate.(FromBerneRM,RubioR:Coronarycirculation.InPageE,ed.Handbook of Physiology: Section 2: The Cardiovascular System: The Heart. Vol1.Bethesda,MD:AmericanPhysiologicalSociety;1979.)18 16 14 12 10 8 6 4 2 20 30 40 50 60 70 80 90 100 110 120 Coronary blood flow (mL/min/100 g) Myocardial oxygen consumption(mL/min/100 g) •Fig. 17.34 ImbalanceintheO2supply–O2demandratioalterscoronarybloodflowbytherateofreleaseofavasodilatormetabolitefromcardiomyocytes.Adecreaseintheratioelicitsanincreaseinvasodilatorrelease,whereasanincreaseintheratiohastheoppositeeffect.
372 SECTION4Berne & Levy Physiology •Fig. 17.35 Schematic Representation of Factors That Increase (+) or Decrease (−) Coronary Vascular Resistance. Intravascularpressure(arterialbloodpressure)stretchesthevesselwall.KATPchannels,adenosinetriphosphate–sensitivepotassiumchannels;NO,nitricoxide;PCO2,partialpressureofcarbondioxide;PO2,partialpressureofoxygen.˜ Myocardial contractile activity Autonomic control Sympathetic nerves: °-Receptors ˛-Receptors Vagus nerves Oxygen supply Myogenic mechanism ˜ Metabolism ˝ Myocardial PO2 KATP channels H2O2 NO Adenosine – + +± + – – – Other metabolic factors PO2, PCO2, H+, K+ Systolic compression activity are complex. A reduction in oxidative metabolism in vascular smooth muscle reduces ATP synthesis, which in turn opens KATP channels and causes hyperpolarization. This change in potential reduces entry of Ca++ and relaxes coronary vascular smooth muscle to increase flow. A reduction in ATP also opens KATP channels in cardiac muscle and generates an outward current that reduces action potential duration and limits Ca++ entry during phase 2 of the action potential. This action may be protective during periods of imbalance between O2 supply and demand. In addition, as cardiac work increases, H2O2 production rises, which activates Kv1.5 channels and thereby causes hyperpolarization of muscle membrane and relaxation of vascular smooth muscle. Moreover, the release of NO and adenosine dilates the arterioles and thereby adjusts the O2 supply to the O2 demand. At low concentrations, adenosine appears to activate endothelial KATP channels and to enhance release of NO. Conversely, at higher concentrations, adenosine acts directly on vascular smooth muscle by activating KATP channels. Decreased O2 demand would sustain the ATP level, as well as reduce the amount of vasodilator substances released, and allows greater expression of basal tone. If production of all these agents is inhibited, coronary blood flow is reduced, both at rest and during exercise. Furthermore, contractile dysfunction and signs of myocardial ischemia become evident.