Responses of the skin microcirculation to acetylcholine and sodium nitroprusside in patients with NIDDM

Abstract

SummaryThe mechanisms involved in the pathogenesis of microangiopathy occurring in non-insulin-dependent diabetes mellitus (NIDDM) are unclear. In the present study, blood flow responses to the vasodilators acetylcholine (which acts via the endothelium) and sodium nitroprusside (a smooth muscle relaxant) were evaluated in this patient group. In 14 male patients with NIDDM, treated with either diet alone (n = 6) or diet plus insulin, (mean age 59 years) and 14 age-pair-matched control subjects, forearm skin perfusion following multiple doses of iontophoretically applied 1% acetylcholine and 0.01% sodium nitroprusside was recorded by laser Doppler perfusion imaging. Basal skin blood flow was not significantly different in the diabetic group compared with the control group. The following results are expressed as drug-minus-vehicle response. Acetylcholine significantly increased forearm skin perfusion (p < 0.001, analysis of variance) in all subjects, but the vasodilatation was attenuated in the patient group compared with control subjects (0.86 + 0.09 vs 1.36 + 0.14 arbitrary units of volts (V) respectively, at the fifth measurement point, mean + SEM, p < 0.01). Skin perfusion significantly increased following sodium nitroprusside (p < 0.001) but was lower in patients than control subjects (0.12 + 0.05 vs 0.45 + 0.11 V, respectively, at the fifth measurement point, p < 0.01). These data suggest that endothelial and/or smooth muscle function may be impaired in the skin microcirculation of patients with NIDDM. [Diabetologia (1995[Diabetologia ( ) 38: 1337[Diabetologia ( -1344 Key words Endothelium, microcirculation, non-insulin-dependent diabetes mellitus, skin, vascular smooth muscle.It has been proposed that haemodynamic factors are involved in the pathogenesis of diabetic microangiopathy [1]. In support of this hypothesis both capillary pressure [2] and capillary filtration coefficient [3] are increased in patients with insulin-dependent diabetes mellitus (IDDM) particularly in those at risk of diabetic nephropathy. The prevalence of microvascular

Noninvasive assessment of endothelial dysfunction in essential hypertension: Comparison of the forearm microvascular reactivity with flow-mediated dilatation of the brachial artery

“…The relative contribution of these factors to cutaneous vasodilation is unclear. Morris et al and Berghoff et al demonstrated that prostanoid-dependent mechanisms do not contribute significantly to endothelium-dependent vasodilation in response to Ach [7,9], whereas Khan et al and Noon et al suggested that forearm cutaneous vasodilation is mediated mainly by prostanoid-dependent mechanism [14,15]. Another problem is the effect of current alone or the effect of drug vehicles.…”

“…Our group and others have used iontophoretic administration of ACh combined with laser Doppler flowmetry to measure microvascular endothelial function in a variety of major cardiovascular diseases, such as atherosclerosis, coronary heart disease, essential hypertension and diabetes [7]. ACh elicits vasodilation through a complex sequence of events: when applied to blood vessels, ACh binds to muscarinic receptors on the surface of endothelial cells, which activates specific G proteins, resulting in the production of NO from L-Arginine (catalysed by NO synthase).…”

“…Iontophoresis coupled with laser Doppler flowmetry makes it possible to assess the real-time changes of the skin blood flow after the administration of different vasoactive substances without systemic effects. Acethylcholine (ACh) given into the skin by iontophoresis causes endothelium dependent vasodilation, which can be compared with the endothelium independent effect of sodium nitroprusside (SNP), an NO donor [7][8][9]. The postocclusive reactive hyperemic response (PORH), mediated mainly by endothelium dependent factors, measurement by laser Doppler flowmetry can be as suitable for the assessment of endothelium dependent vasodilation as the flow-mediated vasodilation of the brachial artery, but on the level of capillaries and arterioles [10].…”

A Laser doppler study of the effect of 2-alkylthio-4-ethyl-4-methyl-4,5 dihydro-1H-imidazolin-5-one oxime (oxime) on the ischaemic rat lower limb

“…Using LDF, leg skin perfusion can be assessed in baseline conditions and in response to different stimuli, such as ischaemia and pharmacological substances (Morris et al, 1995). The LDF results of systemic oxime injection through femoral cannula or its topical application on the planter surface of the rat hind paw showed that it caused significant increase in the post-ischaemic R/L BFR as compared to the pre-drug basal level.…”

Cardiac syndrome X versus metabolic syndrome X

“…They also found that vascular impairment in women with cardiac syndrome X extends to the microvasculature of forearm skin as demonstrated by the noninvasive technique of laser Doppler imaging with iontophoresis [5]. This is a novel technique that has been used to demonstrate impairment at a microvascular level in diabetes [6], hypertension [7] and dyslipidemia [8].…”