Relationship of myocardial metabolism and coronary flow: dependence on extracellular calcium.
The hypothesis that extracellular [Ca2+] ([Ca2+]e) influences the transmission of vasoregulatory information from the heart to coronary smooth muscle was examined. The isolated, retrogradely perfused rat heart was used to evaluate vascular reactivity to transient infusion of either 0.88 mM Amytal (amobarbital), hypoxia (95% N2-5% CO2), or 12 microM adenosine in the presence and absence of 2.5 microM verapamil. Amytal alone enhanced coronary flow by 78% and lactate efflux by 10-fold, whereas it decreased O2 consumption by 40% and the ratio of the free cytosolic concentrations of ATP-to-ADP times the intracellular concentration of inorganic phosphate ([ATP]f/[ADP]f[Pi]) by 10-fold. These responses were attenuated by preperfusion with verapamil, i.e., flow and lactate efflux increased by 4% and fourfold, respectively, and O2 consumption and [ATP]f/[ADP]f/[Pi] decreased by 8% and threefold, respectively, as compared with values attained with verapamil at steady state. Washout of the calcium channel antagonist by perfusion for 55 min with a verapamil-free medium resulted in a return of metabolic variables to control levels. Subsequent infusion of Amytal induced metabolic changes that were similar to those obtained before exposure to the calcium antagonist, but flow rose only by 26%. Vascular responses to hypoxia were similarly modified, whereas those to adenosine were unaffected. Hearts perfused with media containing either low [Ca2+]e or 10 microM diltiazem and exposed to Amytal produced flow patterns analogous to those perfused with verapamil. These data, in part, distinguish changes in vascular resistance that occur in response to cardiac metabolism from those which result from agents with direct action on smooth muscle, in particular, adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
D000255:Adenosine Triphosphate / Q000378:metabolism; D000654:Amobarbital / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003326:Coronary Circulation; D000860:Hypoxia / Q000503:physiopathology; D007473:Ion Channels / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008433:Mathematics; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D007773:Lactates; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D014700:Verapamil; D000654:Amobarbital; D002118:Calcium