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Increased coronary arteriolar contraction to serotonin in juvenile pigs with metabolic syndrome.

Abstract：

:Metabolic syndrome (MetS) is associated with alterations in coronary vascular smooth muscle and endothelial function. The current study examined the contractile response of the isolated coronary arterioles to serotonin in pigs with and without MetS and investigated the signaling pathways responsible for serotonin-induced vasomotor tone. The MetS pigs (8-weeks old) were fed with a hyper-caloric, fat/cholesterol diet and the control animals (lean) were fed with a regular diet for 12 weeks (n = 6/group). The coronary arterioles (90-180 μm in diameter) were dissected from the harvested pig myocardial tissues and the in vitro coronary arteriolar response to serotonin was measured in the presence of pharmacological inhibitors. The protein expressions of phospholipase A2 (PLA2), TXA2 synthase, and the thromboxane-prostanoid (TP) receptor in the pigs' left ventricular tissue samples were measured using Western blotting. Serotonin (10-9-10-5 M) induced dose-dependent contractions of coronary-resistant arterioles in both non-MetS control (lean) and MetS pigs. This effect was more pronounced in the MetS vessels compared with those of non-MetS controls (lean, P < 0.05]. Serotonin-induced contraction of the MetS vessels was significantly inhibited in the presence of the selective PLA2 inhibitor quinacrine (10-6 M), the COX inhibitor indomethacin (10-5 M), and the TP receptor antagonist SQ29548 (10-6 M), respectively (P < 0.05). MetS exhibited significant increases in tissue levels of TXA2 synthase and TP receptors (P < 0.05 vs. lean), respectively. MetS is associated with increased contractile response of porcine coronary arterioles to serotonin, which is in part via upregulation/activation of PLA2, COX, and subsequent TXA2, suggesting that alteration of vasomotor function may occur at an early stage of MetS and juvenile obesity.

journal_name

Mol Cell Biochem

journal_title

Molecular and cellular biochemistry

authors

Lawandy I,Liu Y,Shi G,Zhang Z,Scrimgeour LA,Pavlov V,Jaworski R,Sellke FW,Feng J

doi

10.1007/s11010-019-03589-6

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

57-64

issue

1-2

eissn

0300-8177

issn

1573-4919

pii

10.1007/s11010-019-03589-6

journal_volume

461

pub_type

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Increased coronary arteriolar contraction to serotonin in juvenile pigs with metabolic syndrome.