Effects of the 5-HT2A Receptor Antagonist Sarpogrelate in Diabetic Patients with Complications

Background: The mechanisms responsible for the onset of sensorimotor peripheral diabetic neuropathy (SMPN) remain largely unknown. To address this issue, we studied the relationship between traditional cardiovascular risk factors, parameters of metabolic control, and the presence of SMPN in patients with type 2 diabetes of relatively short duration. Methods: Blood pressure, glycated hemoglobin, lipid profile, and the presence of micro- and macrovascular complications were assessed and monitored in 31 consecutive ambulatory patients with type 2 diabetes (age 60.7 ± 7.5 years, mean ± SD) within 10 years of diagnosis (mean diabetes duration 6.0 ± 2.3 years). Results: Clinical and neurophysiological features of SMPN were present in 10 patients (SMPN+, 32%). There were no significant differences in age, gender distribution, diabetes duration, body mass index, metabolic control, and serum cholesterol between SMPN– and SMPN+ patients. However, the prevalence of hypertension (i.e. blood pressure ≧140/90 mm Hg) was higher in SMPN+ patients (10/10 vs. 13/21, χ^{2 =} 5.13, p = 0.025). Regression analysis showed that, after correcting for age, gender, duration of diabetes, glycated hemoglobin, and cholesterol, the presence of hypertension was independently associated with SMPN (R² = 0.17, p = 0.023). Conclusions: There is a strong association between hypertension and SMPN in type 2 diabetic patients with relatively short duration of disease. This relationship is independent of other risk factors.

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Section: Discussionmentioning

confidence: 99%

Hypertension and Sensorimotor Peripheral Neuropathy in Type 2 Diabetes

2006

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“…Hypertension is also an apparent risk factor for sensory neuropathy (Cohen et al., 1998; Emdin et al., 2015; Hebert et al., 2017; Tesfaye et al., 2005). Data indicate pharmacological reduction in BP results in increased nerve conduction velocities (Hotta et al., 1999; Malik et al., 1998; Reja, Tesfaye, Harris, & Ward, 1995). Reduced NO bioavailability (Holowatz & Kenney, 2007a; Taddei, Virdis, Ghiadoni, Magagna, & Salvetti, 1997) and elevated oxidative stress (Holowatz & Kenney, 2007a; Lassegue & Griendling, 2004; Smith et al., 2011) are hallmarks of hypertension and greatly effect microvascular and endothelial function (Holowatz & Kenney, 2007a, 2007b).…”

Section: Discussionmentioning

confidence: 99%

Cutaneous sensory nerve‐mediated microvascular vasodilation in normotensive and prehypertensive non‐Hispanic Blacks and Whites

et al. 2020

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Relative to non-Hispanic Whites, non-Hispanic Blacks are disproportionately affected by elevated blood pressure (BP). It is unknown whether race or subclinical increases in BP affect the ability of cutaneous sensory nerves to induce cutaneous microvascular vasodilation. Sixteen participants who self-identified as non-Hispanic Black (n = 8) or non-Hispanic White (n = 8) were subgrouped as normotensive or prehypertensive. Participants were instrumented with three intradermal microdialysis fibers: (a) control, (b) 1 μM sodium nitroprusside (SNP), an exogenous nitric oxide (NO) donor, and (c) 20 mM N G -nitro-l-arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor. A slow local heating protocol (33-40°C, 0.1°C/ min) was used to assess the onset of cutaneous sensory nerve-mediated vasodilation (temperature threshold) and skin blood flow was measured using laser-Doppler flowmetry. At control sites, the temperature threshold occurred at a higher temperature in non-Hispanic Blacks (normotensive: 37.2 ± 0.6°C, prehypertensive: 38.9 ± 0.5°C) compared to non-Hispanic Whites (normotensive: 35.2 ± 0.8°C, prehypertensive:35.2 ± 0.9°C). L-NAME shifted the temperature threshold higher in non-Hispanic Whites (normotensive: 37.8 ± 0.7°C, prehypertensive: 38.2 ± 0.8°C), but there was no observed effect in non-Hispanic Blacks. SNP did not affect temperature threshold in non-Hispanic Whites, but shifted the temperature threshold lower in non-Hispanic Blacks (normotensive: 34.6 ± 1.2°C, prehypertensive: 34.8 ± 1.1°C). SNP mitigated differences in temperature threshold across all groups. There was no effect found for BP status in either the non-Hispanic Black or non-Hispanic White groups. These data suggest that reduced NO bioavailability affects the ability of cutaneous sensory nerves to induce microvascular vasodilation in young, otherwise healthy non-Hispanic Blacks. K E Y W O R D S human, nitric oxide, skin How to cite this article: Turner CG, Miller JT, Otis JS, Hayat MJ, Quyyumi AA, Wong BJ. Cutaneous sensory nerve-mediated microvascular vasodilation in normotensive and prehypertensive non-Hispanic Blacks and Whites. Physiol Rep. 2020;8:e14437.

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“…In the United Kingdom Prospective Diabetes Study, control of hypertension not only improved macrovascular outcomes but also reduced the incidence of microvascular complications [31]. Moreover, small studies have shown that treatment with vasodilators such as angiotensin‐converting enzyme inhibitors and 5‐HT 2 antagonists improves NCV [32–34]. Antihypertensive treatment with a specific focus on PP reduction might represent a valuable option for the prevention and management of this disabling complication in type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Pulse pressure is independently associated with sensorimotor peripheral neuropathy in patients with type 2 diabetes

Jarmuzewska

Mangoni

2005

Journal of Internal Medicine

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Abstract. Jarmuzewska EA, Mangoni AA (University of Milan, Milan, Italy; and Flinders University, Adelaide, Australia). Pulse pressure is independently associated with sensorimotor peripheral neuropathy in patients with type 2 diabetes. J Intern Med 2005; 258: 38-44.Objectives. The mechanisms responsible for the onset and progression of sensorimotor peripheral neuropathy (SMPN) in type 2 diabetes remain largely unknown. Although a link between hypertension and SMPN has been observed, it is not clear which blood pressure (BP) component (i.e. systolic, SBP; diastolic, DBP; or pulse pressure, PP) is primarily involved. We sought to determine the relationship between BP components and parameters of nerve function in type 2 diabetes. Design. Cross-sectional study. Setting. Academic medical centre. Subjects. A total of 55 consecutive ambulatory patients with type 2 diabetes (age 62.6 ± 8.0 years, mean ± SD). Interventions. Measurement of clinic BP and 10 neurophysiological parameters: motor nerve conduction velocity (NCV; median, ulnar, posterior tibial and peroneal nerve), sensory amplitude (AMP) and latency (LAT; median, ulnar and sural nerve). Results. Univariate analysis showed that age, diabetes duration, SBP and PP were negatively correlated with nerve function. Regression analysis showed that, after correcting for age, duration of diabetes, glycated haemoglobin, body mass index, microalbuminuria and SBP, PP was independently and negatively associated with NCV (median, P ¼ 0.011; ulnar, P ¼ 0.001; peroneal, P ¼ 0.006 and posterior tibial, P ¼ 0.005) and signal AMP (ulnar, P ¼ 0.027; sural, P ¼ 0.055), and positively associated with signal LAT (median, P ¼ 0.083; sural, P ¼ 0.021). SBP was negatively associated with signal AMP (median, P ¼ 0.012) and positively associated with LAT (ulnar, P ¼ 0.018). By contrast, DBP failed to show any significant correlation with nerve function. Conclusions. The PP is strongly associated with neurophysiological parameters of nerve function in patients with type 2 diabetes. This relationship is independent of traditional risk factors and other BP components.

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Effects of the 5-HT2A Receptor Antagonist Sarpogrelate in Diabetic Patients with Complications

Cited by 12 publications

References 24 publications

Hypertension and Sensorimotor Peripheral Neuropathy in Type 2 Diabetes

Hypertension and Sensorimotor Peripheral Neuropathy in Type 2 Diabetes

Cutaneous sensory nerve‐mediated microvascular vasodilation in normotensive and prehypertensive non‐Hispanic Blacks and Whites

Pulse pressure is independently associated with sensorimotor peripheral neuropathy in patients with type 2 diabetes

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