Effects of carbon monoxide and heme oxygenase inhibitors in cerebral vessels of rats and mice

Jon J. Andresen, Nadeem Shafi, William Durante, Robert M. Bryan

Research output: Contribution to journalArticle

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Abstract

Carbon monoxide (CO) has been postulated to be a signaling molecule in many tissues, including the vasculature. We examined vasomotor responses of adult rat and mouse cerebral arteries to both exogenously applied and endogenously produced CO. The diameter of isolated, pressurized, and perfused rat middle cerebral arteries (MCAs) was not altered by authentic CO (10-6 to 10-4 M). Mouse MCAs, however, dilated by 21 ± 10% at 10 -4 M CO. Authentic nitric oxide (NO·, 10-10 to 10-7 M) dilated both rat and mouse MCAs. At 10-8 M NO·, rat vessels dilated by 84 ± 4%, and at 10-7 M NO·, mouse vessels dilated by 59 ± 9%. Stimulation of endogenous CO production through heme oxygenase (HO) with the heme precursor δ-aminolevulinic acid (10-10 to 10-4 M) did not dilate the MCAs of either species. The metalloporphyrin HO inhibitor chromium mesoporphyrin IX (CrMP) caused profound constriction of the rat MCA (44 ± 2% at 3 × 10-5 M). Importantly, this constriction was unaltered by exogenous CO (10-4 M) or CO plus 10-5 M biliverdine (both HO products). In contrast, exogenous CO (10-4 M) reversed CrMP-induced constriction in rat gracilis arterioles. Control mouse MCAs constricted by only 3 ± 1% in response to 10-5 M CrMP. Magnesium protoporphyrin IX (10-5 M), a weak HO inhibitor used to control for nonspecific effects of metalloporphyrins, also constricted the rat MCA to a similar extent as CrMP. We conclude that, at physiological concentrations, CO is not a dilator of adult rodent cerebral arteries and that metalloporphyrin HO inhibitors have nonspecific constrictor effects in rat cerebral arteries.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number1
DOIs
StatePublished - Jul 13 2006

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Heme Oxygenase (Decyclizing)
Carbon Monoxide
Middle Cerebral Artery
Metalloporphyrins
Cerebral Arteries
Constriction
Biliverdine
Aminolevulinic Acid
Arterioles
Heme
Rodentia
Nitric Oxide

All Science Journal Classification (ASJC) codes

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

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Effects of carbon monoxide and heme oxygenase inhibitors in cerebral vessels of rats and mice. / Andresen, Jon J.; Shafi, Nadeem; Durante, William; Bryan, Robert M.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 291, No. 1, 13.07.2006.

Research output: Contribution to journalArticle

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abstract = "Carbon monoxide (CO) has been postulated to be a signaling molecule in many tissues, including the vasculature. We examined vasomotor responses of adult rat and mouse cerebral arteries to both exogenously applied and endogenously produced CO. The diameter of isolated, pressurized, and perfused rat middle cerebral arteries (MCAs) was not altered by authentic CO (10-6 to 10-4 M). Mouse MCAs, however, dilated by 21 ± 10{\%} at 10 -4 M CO. Authentic nitric oxide (NO·, 10-10 to 10-7 M) dilated both rat and mouse MCAs. At 10-8 M NO·, rat vessels dilated by 84 ± 4{\%}, and at 10-7 M NO·, mouse vessels dilated by 59 ± 9{\%}. Stimulation of endogenous CO production through heme oxygenase (HO) with the heme precursor δ-aminolevulinic acid (10-10 to 10-4 M) did not dilate the MCAs of either species. The metalloporphyrin HO inhibitor chromium mesoporphyrin IX (CrMP) caused profound constriction of the rat MCA (44 ± 2{\%} at 3 × 10-5 M). Importantly, this constriction was unaltered by exogenous CO (10-4 M) or CO plus 10-5 M biliverdine (both HO products). In contrast, exogenous CO (10-4 M) reversed CrMP-induced constriction in rat gracilis arterioles. Control mouse MCAs constricted by only 3 ± 1{\%} in response to 10-5 M CrMP. Magnesium protoporphyrin IX (10-5 M), a weak HO inhibitor used to control for nonspecific effects of metalloporphyrins, also constricted the rat MCA to a similar extent as CrMP. We conclude that, at physiological concentrations, CO is not a dilator of adult rodent cerebral arteries and that metalloporphyrin HO inhibitors have nonspecific constrictor effects in rat cerebral arteries.",
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