Andresen Jon J, Shafi Nadeem I, Durante William, Bryan Robert M
Department of Anesthesiology, Baylor College of Medicine, Houston, TX 77030, USA.
Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H223-30. doi: 10.1152/ajpheart.00058.2006. Epub 2006 Feb 17.
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 delta-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.
一氧化碳（CO）被假定为包括脉管系统在内的许多组织中的一种信号分子。我们研究了成年大鼠和小鼠脑动脉对外源性施加和内源性产生的CO的血管舒缩反应。分离、加压并灌注的大鼠大脑中动脉（MCA）的直径未因纯CO（10⁻⁶至10⁻⁴M）而改变。然而，小鼠MCA在10⁻⁴M CO时扩张了21±10%。纯一氧化氮（NO，10⁻¹⁰至10⁻⁷M）使大鼠和小鼠的MCA均扩张。在10⁻⁸M NO时，大鼠血管扩张了84±4%，在10⁻⁷M NO时，小鼠血管扩张了59±9%。用血红素前体δ-氨基乙酰丙酸（10⁻¹⁰至10⁻⁴M）通过血红素加氧酶（HO）刺激内源性CO产生并未使两种动物的MCA扩张。金属卟啉HO抑制剂中卟啉铬IX（CrMP）导致大鼠MCA显著收缩（在3×10⁻⁵M时为44±2%）。重要的是，这种收缩不受外源性CO（10⁻⁴M）或CO加10⁻⁵M胆绿素（两者均为HO产物）的影响。相反，外源性CO（10⁻⁴M）可逆转CrMP诱导的大鼠股薄肌小动脉收缩。对照小鼠MCA对10⁻⁵M CrMP的反应仅收缩3±1%。镁原卟啉IX（10⁻⁵M），一种用于控制金属卟啉非特异性作用的弱HO抑制剂，也使大鼠MCA收缩至与CrMP相似的程度。我们得出结论，在生理浓度下，CO不是成年啮齿动物脑动脉的扩张剂，并且金属卟啉HO抑制剂在大鼠脑动脉中具有非特异性收缩作用。
