Canine coronary microvessel NO production regulates oxygen consumption in ecNOS knockout mouse heart

J Mol Cell Cardiol. 2000 Jul;32(7):1141-6. doi: 10.1006/jmcc.2000.1154.

Abstract

We have previously shown that NO production by tissues following stimulation with bradykinin or other agonists can regulate oxygen consumption in skeletal muscle, heart and kidney. From those studies and from those using agonists, which classically release NO from blood vessels and which are unable to regulate tissue oxygen consumption in heart from ecNOS knockout mice, we concluded that vascular NO production is capable of regulating tissue oxygen consumption. The goal of these studies was to directly address the concept that NO production by blood vessels can regulate tissue oxygen consumption using a classical transfer paradigm. Microvessels, capable of producing NO, were prepared from canine hearts using a sieving technique, cardiac tissue was taken from mice lacking the ability to produce NO from ecNOS (ecNOS -/- mice) and tissue oxygen consumption measured in vitro using a Clark type electrode in a sealed chamber. Bradykinin (10(-7)to 10(-4)M) had no effect on tissue oxygen consumption when administered to heart from ecNOS -/mice as expected and no effect on oxygen consumption by isolated canine coronary microvessels (0+/-5% at 10(-5)M). However when coronary microvessels were co-incubated with heart from ecNOS -/- mice, bradykinin caused a dose dependent reduction in tissue oxygen consumption reaching a maximum of 44+/-10% at 10(-4)M. The effects of bradykinin were entirely abolished by L -NAME. The calculated concentration range for NO in these studies was 2.9 to 293 n M, within estimated physiologic range for the activity of NO on cytochrome oxidase. These data indicate that coronary microvessels can regulate cardiac oxygen consumption through a NO dependent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bradykinin / pharmacology
  • Culture Techniques
  • Dogs
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / enzymology*
  • Enzyme Inhibitors / pharmacology
  • Male
  • Mice
  • Mice, Knockout
  • Microcirculation / enzymology*
  • Myocardium / enzymology*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase / physiology
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Organ Size
  • Oxygen Consumption*

Substances

  • Enzyme Inhibitors
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Bradykinin
  • NG-Nitroarginine Methyl Ester