Microvascular dysfunction as a link between obesity, insulin resistance and hypertension

Abstract

Impaired microvascular dilatation from any cause and impaired insulin-mediated capillary recruitment in particular result in suboptimal delivery of glucose and insulin to skeletal muscle, and subsequently impairment of glucose disposal (insulin resistance). In addition, microvascular dysfunction, through functional and/or structural arteriolar and capillary drop-out, and arteriolar constriction, increases peripheral resistance and thus blood pressure. Microvascular dysfunction may thus constitute a pathway that links insulin resistance and hypertension. Overweight and obesity may be an important cause of microvascular dysfunction. Mechanisms linking overweight and obesity to microvascular dysfunction include changes in the secretion of adipokines leading to increased levels of free fatty acids and inflammatory mediators, and decreased levels of adiponectin all of which may impair endothelial insulin signaling. Microvascular dysfunction may thus constitute a new treatment target in the prevention of type 2 diabetes mellitus and hypertension.

Acute Hyperglycemia Impairs Vascular Function in Healthy and Cardiometabolic Diseased Subjects

“…14 In normal vascular function, the endothelium and vascular smooth muscle (VSM) cells continuously interact to regulate vasodilation and vasoconstriction, maintaining optimal organ perfusion and vascular tone. 15,16 During acute hyperglycemia, increased oxidative stress has been proposed as a key trigger of vascular dysfunction by reducing nitric oxide (NO) production or NO bioavailability. 15,17,18 Furthermore, animal and in vitro studies suggest that acute hyperglycemia may also impair VSM function by disrupting VSM cell apoptosis, causing subsequent VSM cell proliferation and desensitization to NO.…”

Impact of high dose n-3 polyunsaturated fatty acid treatment on measures of microvascular function and vibration perception in non-alcoholic fatty liver disease: results from the randomised WELCOME trial

“…These findings and our data, taken together, suggest strongly that peripheral neurological function is more closely associated with a measure of microvascular health than with metabolic risk factors, with the exception of IR. Microvascular dysfunction has been proposed to be a link between obesity, IR and hypertension [33], and a reduced microvascular dilator and exchange capacity has consistently been reported by us and by others in individuals with features of the metabolic syndrome [34][35][36][37]. With respect to a link between VPT and HOMA-IR, it is important to note that the DHA+EPA intervention did not improve HOMA-IR (data not shown but available from the authors).…”

Introductory Chapter: Microcirculation in Health and Disease

“…In this respect, vasoactive compounds affecting vascular tone and perfusion could also indirectly affect the metabolism. Insufficient perfusion might in turn lead to deranged metabolic pathways making one more susceptible to metabolic diseases, such as diabetes and obesity [9]. Interestingly, nitric oxide (NO) as a key endothelial vasodilator also directly affects metabolism by competing with mitochondria for oxygen and consequently inhibiting the oxidative phosphorylation and potentially switching the metabolism to some other (anaerobic) pathways [10].…”