Carbon Monoxide in Chronic Uraemia Related to Erythropoietin Treatment and Smoking Habits

Abstract

In 69 patients on chronic haemodialysis, blood sampled randomly during dialysis was analyzed for carboxyhaemoglobin (COHb). The median value was 1.40% (range 0.9-2.3) in non-smoking patients and (1.4-7.5) in smokers. In non-smokers treated with erythropoietin (EPO) correlation was found between COHb and the weekly EPO dose (r = 0.57, p = 0.007). In smoking patients not given EPO, the COHb correlated well with the number of cigarettes smoked (r = 0.84, p = 0.003). The COHb values did not correlate to the haemoglobin values. It is concluded that COHb levels in uraemic non-smokers are elevated because of increased endogenous CO production from the enhanced erythrocyte turnover. As even low COHb levels may negatively influence the oxygen status of the uraemic patient, the addition of exogenous CO from cigarette smoking should be avoided.

Carbon Monoxide-Induced Vasorelaxation and the Underlying Mechanisms

“…The inhibitory eects of Rp-8-Br-cyclicGMPS on the CO-induced vasorelaxation were not dierent between the two concentration levels (P40.05). This lends support to the notion that the maximum inhibition of cyclicGMP-dependent protein kinase (PKG) might have been achieved with 30 mM Rp-8-Br-cyclicGMPS (Romey et al, 1984;Thunedborg et al, 1995). The CO-induced relaxations of the vascular tissues pretreated with Rp-8-Br-cyclicGMPS plus MB and the tissues pretreated with Rp-8-Br-cyclicGMPS alone were also not signi®cantly dierent (Figure 4), further supporting the contention that maximal inhibition of the cyclicGMP pathway was produced by Rp-8-Br-cyclicGMPS at 30 mM.…”

“…We established a bioassay, in the present study, to monitor indirectly the vascular eect of endogenously generated CO. Our results represent the ®rst observation that endogenously generated CO plays a signi®cant modulatory role in the regulation of vascular contractile responses. Since signi®cant changes in the generation of endogenous CO have been observed in dierent pathophysiological situations, such as hypoxia (Morita et al, 1995), subarachnoid haemorrhage (Matz et al, 1996), hypertension (Levere et al, 1990) or chronic uraemia (Thunedborg et al, 1995), our results may also help to understand better these CO-related vascular abnormalities.…”

“…These studies emphasize the resemblance of CO to nitric oxide (NO), another endogenous gaseous vasorelaxant factor. Considering that the physiological vascular eect of NO has been ®rmly established, CO is proposed to perform both physiologically (Furchgott & Jothianandan, 1991) and pathophysiologically (Levere et al, 1990;Thunedborg et al, 1995) vasoactive functions.…”

Reduced Vasorelaxant Effect of Carbon Monoxide in Diabetes and the Underlying Mechanisms

“…Altered metabolism or vascular actions of CO in many cases are coupled to cardiovascular diseases. For instance, the increased endogenous production of CO was reported in chronic uremic patients (10). Increased HO-1 expression and activity in hypoxia, ischemia-reperfusion, and subarachnoid hemorrhage have also been reported (1).…”

“…The production of CO from vascular tissues has also been directly measured (7). These studies emphasize the importance of CO as an endogenous vasorelaxant factor under physiological (8) or pathophysiological (9,10) conditions. The elevation of cellular cGMP levels and the opening of plasma membrane K + channels are the main mechanisms that have been proposed to explain the vascular effects of CO. CO may increase cGMP content via its stimulatory interaction with the heme in the regulatory subunit of guanylyl cyclase.…”