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

1 Department of Anesthesiology and 2 Section of Pediatric Critical Care, Baylor College of Medicine, Houston, Texas; and 3 Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri-Columbia, Columbia, Missouri Submitted 13 January 2006 ; accepted in final form 12 February 2006 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 -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 x 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. cerebral arteries; chromium mesoporphyrin; endothelium-derived hyperpolarization factor; gracilis arteriole Address for reprint requests and other correspondence: J. J. Andresen, Dept. of Anesthesiology, Baylor College of Medicine, One Baylor Plaza, Suite 434D, Houston, TX 77030 (e-mail: andresen{at}bcm.tmc.edu )