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.

• Authors: Isabella Lawandy, Yuhong Liu, Guangbin Shi, Zhiqi Zhang, Laura A Scrimgeour, Vasile Pavlov, Reed Jaworski, Frank W Sellke, Jun Feng
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 461 Issue 1-2 Pg. 57-64 (Nov 2019) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 31352610 (Publication Type: Journal Article)

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Fatty Acids, Unsaturated
• Hydrazines
• Receptors, Thromboxane
• Serotonin
• Thromboxane A2
• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• SQ 29548
• Prostaglandin-Endoperoxide Synthases
• Phospholipases A2
• Quinacrine
• Indomethacin

Topics

• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid (pharmacology)
• Animals
• Arterioles (drug effects, physiopathology)
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
• Coronary Vessels (drug effects, physiopathology)
• Disease Models, Animal
• Fatty Acids, Unsaturated (pharmacology)
• Hydrazines (pharmacology)
• Indomethacin (pharmacology)
• Male
• Metabolic Syndrome (physiopathology)
• Phospholipases A2 (metabolism)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Quinacrine (pharmacology)
• Receptors, Thromboxane (metabolism)
• Serotonin (pharmacology)
• Swine
• Thromboxane A2 (metabolism)
• Vasoconstriction (drug effects)