The effect of kisspeptin on the regulation of vascular tone

Abstract

Kisspeptin has been implicated in cardiovascular control. Eicosanoids play a crucial role in the activation of platelets and the regulation of vascular tone. In the present study, we investigated the effect of kisspeptins on eicosanoid synthesis in platelets and aorta in vitro. Platelets and aorta were isolated from Wistar-Kyoto rats. After preincubation with different doses of kisspeptin, samples were incubated with [1-(14)C]arachidonic acid (0.172 pmol/mL) in tissue culture Medium 199. The amount of labeled eicosanoids was measured with liquid scintillation, after separation with overpressure thin-layer chromatography. Kisspeptin-13 stimulated the thromboxane synthesis. The dose-response curve was bell-shaped and the most effective concentration was 2.5 × 10(-8) mol/L, inducing a 27% increase. Lipoxygenase products of platelets displayed a dose-dependent elevation up to the dose of 5 × 10(-8) mol/L. In the aorta, kisspeptin-13 induced a marked elevation in the production of 6-keto-prostaglandin F1α, the stable metabolite of prostacyclin, and lipoxygenase products. Different effects of kisspeptin on cyclooxygenase and lipoxygenase products indicate that beyond intracellular Ca(2+) mobilization, other signaling pathways might also contribute to its actions. Our data suggest that kisspeptin, through the alteration of eicosanoid synthesis in platelets and aorta, may play a physiologic and (or) pathologic role in the regulation of vascular tone.

Potent Vasoconstrictor Kisspeptin‐10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist

“…31 KPs also regulate vascular tone as a constrictor. 32 However, in our study, chronic infusion of KP-10 did not affect body weight, plasma glucose level, and BP in ApoE À/À mice. Pentraxin-3 is well known to reflect vascular inflammation derived from mainly ECs followed by VSMCs and macrophages and also is associated with apoptosis and plaque vulnerability.…”

“…Actually, kiss1r ‐knockout mice exhibit the phenotypes of glucose intolerance and obesity . KPs also regulate vascular tone as a constrictor . However, in our study, chronic infusion of KP‐10 did not affect body weight, plasma glucose level, and BP in ApoE −/− mice.…”

Effects of kisspeptin on diabetic rat platelets

“…This was detected when KP-13 was applied intraperitoneally in vivo (Qureshi and Kanwal 2011). In our earlier experiments we detected an enhancement of thromboxane (a potent vasoconstrictor and platelet aggregator) synthesis of rat platelets in the presence of KP-13 (Mezei et al 2015). In our present study, we observed that KP-13 enhanced the aggregation of nondiabetic platelets in a dosedependent manner, in the presence of collagen as inducer.…”

“…In our earlier experiments, we detected an elevated eicosanoid synthesis of rat platelets in the presence of KP-13 (Mezei et al 2015).…”

“…(1-adamantane carbonyl-Arg-Phe-NH 2 ) is a synthetic peptide that might have a potentially antagonistic effect on KP-13 (Simonin et al 2006). KPs can participate in the regulation of the reproductive axis (Colledge 2009), the cardiovascular system (Maguire et al 2011;Mead et al 2007;Mezei et al 2015;Sawyer et al 2011), hemostasis (Qureshi and Kanwal 2011), food intake (Dudek et al 2016;Hussain et al 2015;Rao et al 2013;Tolson et al 2014;Wahab et al 2013), and various metabolic pathways (Silvestre et al 2008;Song et al 2014).…”