Experimental physiology
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Experimental physiology · Jun 2019
Reduced insulin sensitivity in young, normoglycaemic subjects alters microvascular tissue oxygenation during postocclusive reactive hyperaemia.
What is the central question of the study? Are measures of reduced insulin sensitivity in young, normoglycaemic subjects correlated with near-infrared spectroscopy-derived microvascular responsiveness [tissue oxygen saturation reperfusion rate (STO2 upslope)] during postocclusive reactive hyperaemia? What is the main finding and its importance? A sevenfold range of hepatic insulin sensitivity is significantly correlated (r = 0.44, P = 0.02) with STO2 upslope after transient tissue ischaemia. Near-infrared spectroscopy may be an important tool for determining altered microvascular function before onset of hyperglycaemia. Identification of pre-type 2 diabetes much earlier than with the present clinical criteria is important for pre-emptive measures against microvascular deterioration. ⋯ Near-infrared spectroscopy (NIRS) measurement of postocclusive reactive hyperaemia (PORH) tissue oxygen saturation reperfusion rate [STO2 upslope (as a percentage per minute)] has recently been correlated with the percentage of flow-mediated dilatation (%FMD). Cardiovascular disease is associated with impairments in %FMD. Reduced insulin sensitivity may negatively affect the vascular system for many years before prediabetes/type 2 diabetes states. The aim of this study was to determine whether static and dynamic STO2 parameters during PORH are correlated with reduced insulin sensitivity in young, normoglycaemic subjects. Glucose and insulin were measured during an oral glucose tolerance test in 18- to 26-year-old, healthy subjects (11 men and 11 women), and STO2 was measured during PORH of antebrachial muscle. Hepatic (ISIHOMA ) and whole-body (ISICOMP ) insulin sensitivities were calculated. The STO2 upslope was negatively correlated with minimal STO2 (r = -0.5, P = 0.01). The change of STO2 from minimum to baseline (ΔSTO2 ) was significantly negatively correlated with fasting insulin (r = -0.5, P = 0.01) and a positively correlated with ISIHOMA (r = 0.65, P = 0.001). The minimum STO2 was significantly negatively correlated with ISIHOMA , and STO2 upslope was significantly positively correlated with ISIHOMA (r = 0.44, P = 0.02). The minimum STO2 (a measure of O2 extraction while the cuff was inflated), ΔSTO2 (a measure of the amount of reperfusion) and STO2 upslope (a measure of responsiveness of the microcirculation to ischaemia) were all positively correlated with ISIHOMA , one of the longest-used measures of insulin sensitivity. The NIRS-derived STO2 might be a useful tool for assessing how levels of reduced insulin sensitivity in young, normoglycaemic adults affect the microvasculature.
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Experimental physiology · Jun 2019
Increased caveolin-1 expression enhances the receptor-operated Ca2+ entry in the aorta of two-kidney, one-clip hypertensive rats.
What is the central question of this study? The aim was to examine and compare the contributions of caveolin-1 to the contractile responses mediated by L-type voltage-dependent calcium channels, store-operated Ca2+ channels and receptor-operated Ca2+ channels in two different types of arteries from two-kidney, one-clip hypertensive rats. What is the main finding and its importance? We demonstrated that the density of caveolae and caveolin-1 expression were significantly upregulated in the aorta of two-kidney, one-clip hypertensive rats, but not in the third-order branches of mesenteric arteries. We highlight that caveolin-1 plays an important role in aortic constriction by enhancing receptor-operated Ca2+ entry in the hypertensive rat model. ⋯ Calcium and its multiple regulatory mechanisms are crucial for the development of hypertension. Among these regulatory mechanisms, store-operated Ca2+ entry (SOCE) and receptor-operated Ca2+ entry (ROCE) mediate agonist-induced calcium influx, contributing to vascular contraction. The SOCE and ROCE are regulated by a variety of mechanisms involving caveolin-1 (Cav1), which has been found to be strongly associated with hypertension in gene polymorphism. In the present study, we investigated the role of Cav1 during the enhanced activity of calcium channels in hypertensive arteries. We demonstrated that the expression level of Cav1 was significantly increased in the aorta of two-kidney, one-clip (2K1C) hypertensive rats. The disruption of caveolae by methyl-β-cyclodextrin did not cause a marked difference in agonist-induced vasoconstriction in the third-order branches of the mesenteric arteries but strongly suppressed the aortic contractile response to endothelin-1 in the 2K1C group, which was not found in the control group. The increase in Cav1 by introduction of Cav1 scaffolding domain enhancing peptide promoted the 1-oleoyl-2-acetyl-glycerol-induced ROCE in hypertensive aortic smooth muscle cells but did not enhance the cyclopiazonic acid-induced SOCE. In the resistance arteries, similar changes were not observed, and no statistical changes of Cav1 expression were evident in the third-order branches of the mesenteric arteries. Our results indicate that increased Cav1 expression might promote the altered [Ca2+ ]i -induced aortic vasoreactivity by enhancing ROCE and be involved in the pathogenesis of hypertension.