Elevation of intracellular calcium in smooth muscle causes endothelial cell generation of NO in arterioles.
It is well known that vascular smooth muscle tone can be modulated by signals arising in the endothelium (e.g., endothelium-derived relaxing factor, endothelium-derived hyperpolarizing factor, and prostaglandins). Here we show that during vasoconstriction a signal can originate in smooth muscle cells and act on the endothelium to cause synthesis of endothelium-derived relaxing factor. We studied responses to two vasoconstrictors (phenylephrine and KCl) that act by initiating a rise in smooth muscle cell intracellular Ca2+ concentration ([Ca2+]i) and exert little or no direct effect on the endothelium. Fluo-3 was used as a Ca2+ indicator in either smooth muscle or endothelial cells of arterioles from the hamster cheek pouch. Phenylephrine and KCl caused the expected rise in smooth muscle cell [Ca2+]i that was accompanied by an elevation in endothelial cell [Ca2+]i. The rise in endothelial cell [Ca2+]i was followed by increased synthesis of NO, as evidenced by an enhancement of the vasoconstriction induced by both agents after blockade of NO synthesis. The molecule involved in signal transmission from smooth muscle to endothelium is as yet unknown. However, given that myoendothelial cell junctions are frequent in these vessels, we hypothesize that the rise in smooth muscle cell Ca2+ generates a diffusion gradient that drives Ca2+ through myoendothelial cell junctions and into the endothelial cells, thereby initiating the synthesis of NO.
Dora
K A
KA
Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, P.O. Box 10011, Charlottesville, VA 22906-0011, USA.
Doyle
M P
MP
Duling
B R
BR
D000109:Acetylcholine / Q000494:pharmacology; D000814:Aniline Compounds; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008647:Mesocricetus; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D010656:Phenylephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D015398:Signal Transduction; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014966:Xanthenes
D000814:Aniline Compounds; D014662:Vasoconstrictor Agents; D014966:Xanthenes; D010656:Phenylephrine; C059715:Fluo-3; D009569:Nitric Oxide; D011189:Potassium Chloride; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester