Clarification of serotonin‐induced effects in peripheral artery disease observed through the femoral artery response in models of diabetes and vascular occlusion: The role of calcium ions

Abstract

Recent findings have demonstrated that serotonin is an important participant in the development and progression of peripheral artery diseases. Taking this into consideration, the goals of this study were to investigate the effects of serotonin on isolated Wistar rat femoral arteries in both healthy and diabetic animals, with and without artery occlusion, with a particular focus on determining the role of calcium in this process. Contraction experiments with serotonin on intact and denuded femoral artery rings, in the presence or absence of nifedipine and ouabain (both separately, or in combination), as well as Ca -free Krebs-Ringer bicarbonate solution were performed. The serotonin-induced results were concentration dependent, but only in healthy animals. The endothelium-dependent contraction of the femoral artery was assessed. In healthy animals, the endothelium-reliant part of contraction was dependent on the extracellular calcium, while the smooth muscle-related part was instead dependent on the intracellular calcium. In diabetic animals, both nifedipine and ouabain influenced serotonin-induced vascular effects by blocking intracellular calcium pathways. However, this was diminished after the simultaneous administration of both blockers.

Senescent murine femoral arteries undergo vascular remodelling associated with accelerated stress‐induced contractility and reactivity to nitric oxide

“…The femoral artery (FA) is a large conduit vessel from the lower limb circulation, formed in humans after completion of the iliofemoral system. Like in other mammalian conduit vessels, it responds to various contractile stimuli, i.e., α 1 ‐adrenoreceptor agonists, 5‐hydroxythryptamin, endothelin‐1, eicosanoids, NO inhibition, etc 4–8 . It is common knowledge that basal and agonist‐induced contractility of the FA could be altered by pathological conditions such as hypoxia, gram‐negative bacterial endotoxins, diabetes or microgravity 5,9–11 .…”

“…Like in other mammalian conduit vessels, it responds to various contractile stimuli, i.e., α 1 -adrenoreceptor agonists, 5-hydroxythryptamin, endothelin-1, eicosanoids, NO inhibition, etc. [4][5][6][7][8] It is common knowledge that basal and agonist-induced contractility of the FA could be altered by pathological conditions such as hypoxia, gram-negative bacterial endotoxins, diabetes or microgravity. 5,[9][10][11] Augmented vascular tone often coincides with advanced age, as at present, it is well appreciated that ageing increases muscle sympathetic nerve activity.…”

Vascular Occlusion Restores Endothelium-Dependent Effects of Adenosine Previously Diminished by Diabetes: The Preliminary Report

“…In the first part of this study, adenosine produced the concentration-dependent relaxation of the rat FA in all of the groups/subgroups. This response of FA was not surprising, since it is well known that adenosine mainly produces vasorelaxant effects [1,19,20]. The adenosine-induced relaxation was endothelium-dependent in all of the groups/subgroups, except in a group of animals with alloxaninduced diabetes.…”

Serotonin-Mediated Activation of Serotonin Receptor Type 1 Oppositely Modulates Voltage-Gated Calcium Channel Currents in Rat Sensory Neurons Innervating Hindlimb Muscle

“…The monoamine neurotransmitter serotonin (5-HT) regulates a number of physiological and pathophysiological processes (Watts et al, 2012;De Ponti, 2004;Švob Štrac et al, 2016;Hornung, 2003), and is known to play an important role in the development and progression of peripheral artery disease (PAD) (Stojanović et al, 2017). In fact, a recent study found that 5-HT serum levels were markedly elevated in PAD patients (Senol and Es, 2015), implying it may play a role in the development and/or progression of this disease.…”