Sympathetic neuronal activity in diabetic and non-diabetic subjects with peripheral arterial occlusive disease

Abstract

Despite the vasoconstrictory influence of the alpha-adrenergic system on the peripheral blood circulation the results of the sympathectomy were not satisfying in the therapy of peripheral arterial occlusive disease (PAOD). The aim of the present investigation was to clarify the pathophysiologic mechanisms of this clinical observation. Free and sulfoconjugated catecholamines were determined in the femoral artery, vein, and cubital vein of 19 healthy controls, 21 non-diabetic patients with PAOD stage II, 8 non-diabetic (PAOD IV) and 20 diabetic patients (D IV) with PAOD stage IV. In comparison with controls and group PAOD II an increased sympathoneuronal tone in group PAOD IV was evident at rest. Sympathetic activation was not restricted to the affected limb, since femoral and cubital venous norepinephrine levels were not different and plasma epinephrine fractional extraction (PEFE) was not altered by angiopathy. The lower sympathoneuronal activation in the group D IV may be attributed to an impaired pain perception or a reduced dopamine beta-hydroxylase activity indicated by a lower ratio of norepinephrine to dopamine. The failing long-term efficacy of lumbar sympathectomy in critical arterial limb disease may be explained by marked spontaneous sympathicolysis in diabetics, whereas in non-diabetics with sympathetic activation other mechanisms like development of unilateral Mönckeberg sclerosis, progression of proximal arterial occlusion or induction of steal effects have to be discussed.

α‐Adrenergic inhibition increases collateral circuit conductance in rats following acute occlusion of the femoral artery

“…13). This implies that during exercise the same, or higher sympathetic activity as noted with vascular insufficiency (Huber et al 1991), would be as effective at vasoconstriction in the ischaemic as in the non‐ischaemic hindlimb. Interestingly, Sapienza et al (1996) observed an exaggerated vasoconstriction attributed to an upregulation of both α 1 ‐ and α 2 ‐receptors in the distal femoral artery following proximal occlusion and reperfusion of the artery.…”

“…Further, if the distal resistance vessels exhibit aberrant dilatation or constriction responses, the utility of the collateral circuit would be in jeopardy. These untoward responses are plausible, since patients with peripheral arterial insufficiency typically have abnormal vessels complicated by atherogenesis, exaggerated responses of distal vessels to noradrenaline (Coats & Hillier, 2000; Jarajapu et al 2001), and heightened sympathetic discharge at rest (Huber et al 1991) and on exertion, as evident by hypertension (Yang & Feng, 2000; Bakke et al 2007). Whether these factors exacerbate the consequences of an already limited blood flow in patients with peripheral arterial insufficiency or whether removal of this exaggerated sympathetic discharge improves exercise capacity, remains to be determined.…”

Effects of aging and type 2 diabetes on resting and post occlusive hyperemia of the forearm; the impact of rosiglitazone

“…Normally, with the arm at rest, there is always both tonic vasoconstrictor and vasodilator tone to the vascular endothelial cells. In the skin, for example, there is a slow tonic release of norepinephrine, a vasoconstrictor, and acetylcholine, a vasodilator [21-23]. If there is an increase in vasoconstrictor activity, then vasoconstriction predominates and if more vasodilator activity is present, then vasodilatation predominates [24].…”

Exercise Training and Peripheral Arterial Disease

“…Whether there are also adaptive changes induced within the central cardiovascular control centers, that could ameliorate or exacerbate conditions in PAD patients, is unknown. Thus, it may be hypothesized that PAD patients are at risk of hypertension during activity and that this elevated afferent nerve traffic could cause neural adaptations which ‘bias’ central neural cardiovascular control and lead to a hyper sympathetic state even at rest, which has been observed (419). The added risks of premature death and morbidity, due to a hypersympathetic condition, have been well recognized (260).…”