Carbon monoxide and cerebral microvascular tone in newborn pigs

Charles Leffler, Alberto Nasjletti, Changhua Yu, Robert A. Johnson, Alexander L. Fedinec, Nicole Walker

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

The present study addresses the hypothesis that CO produced from endogenous heme oxygenase (HO) can dilate newborn cerebral arterioles. HO-2 protein was highly expressed in large and small blood vessels, as well as parenchyma, of newborn pig cerebrum. Topically applied CO dose-dependently dilated piglet pial arterioles in vivo over the range 10-11-10-9 M (maximal response). CO-induced cerebrovascular dilation was abolished by treatment with the Ca2+-activated K+ channel inhibitors tetraethylammonium chloride and iberiotoxin. The HO substrate heme-L-lysinate also produced tetraethylammonium-inhibitable, dose-dependent dilation from 5 x 10-8 to 5 x 10-7 M (maximal). The HO inhibitor chromium mesoporphyrin blocked dilation of pial arterioles in response to heme-L-lysinate. In addition to inhibiting dilation to heme-L-lysinate, chromium mesoporphyrin also blocked pial arteriolar dilations in response to hypoxia but did not alter responses to hypercapnia or isoproterenol. We conclude that CO dilates pial arterioles via activation of Ca2+-activated K+ channels and that endogenous HO-2 potentially can produce sufficient CO to produce the dilation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume276
Issue number5 45-5
StatePublished - May 1 1999

Fingerprint

Carbon Monoxide
Dilatation
Swine
Arterioles
Heme Oxygenase (Decyclizing)
Calcium-Activated Potassium Channels
Tetraethylammonium
Hypercapnia
Cerebrum
Isoproterenol
Blood Vessels
heme lysinate
Proteins

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Leffler, C., Nasjletti, A., Yu, C., Johnson, R. A., Fedinec, A. L., & Walker, N. (1999). Carbon monoxide and cerebral microvascular tone in newborn pigs. American Journal of Physiology - Heart and Circulatory Physiology, 276(5 45-5).

Carbon monoxide and cerebral microvascular tone in newborn pigs. / Leffler, Charles; Nasjletti, Alberto; Yu, Changhua; Johnson, Robert A.; Fedinec, Alexander L.; Walker, Nicole.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 276, No. 5 45-5, 01.05.1999.

Research output: Contribution to journalArticle

Leffler, C, Nasjletti, A, Yu, C, Johnson, RA, Fedinec, AL & Walker, N 1999, 'Carbon monoxide and cerebral microvascular tone in newborn pigs', American Journal of Physiology - Heart and Circulatory Physiology, vol. 276, no. 5 45-5.
Leffler, Charles ; Nasjletti, Alberto ; Yu, Changhua ; Johnson, Robert A. ; Fedinec, Alexander L. ; Walker, Nicole. / Carbon monoxide and cerebral microvascular tone in newborn pigs. In: American Journal of Physiology - Heart and Circulatory Physiology. 1999 ; Vol. 276, No. 5 45-5.
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