Activation of TP receptors induces high release of PGI(2) in coronary arteries of renal hypertensive rats

Author(s)

Paula, T. D. ^[1] ; Silva, B. R. ^[1] ; Grando, M. D. ^[1] ; Souza, H. C. D. ^[2] ; Bendhack, L. M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY; v. 122, p. 125-133, SEP 2018.
• Web of Science Citations: 1

Abstract

Aim: To investigate the molecular mechanisms and cellular signaling pathways involved in the activation of TP receptors and the consequent induction of contractile responses in coronary arteries of renal hypertensive (2K-1C) rats. Methods and results: The coronary perfusion pressure (CPP) was lower in 2K-1C rats during increased coronary flow as measured by the Langendorff technique. The coronary contraction and relaxation were evaluated by vascular reactivity studies, and the molecular mechanisms were investigated on the basis of the protein expression of TP receptors, Cav-1, eNOS, COX-1, and COX-2, as measured by Western blot. The levels of eicosanoids were determined by ELISA immunoassay and analyzed by reverse-phase HPLC coupled to electrospray ionization mass spectrometry (HPLC-MS/MS). The metabolites from NO production were evaluated by the Griess reaction. The coronary arteries of 2K-1C rats expressed COX-2 to a larger extent and TP receptors to a lesser extent than the coronary arteries of normotensive (2K) rats. Selective COX-1 and non-selective COX inhibitors reversed the reduction in the contraction induced by TP receptors in the coronary arteries of 2K-1C rats. U46619, an agonist of TP receptors, induced a contractile response that was relaxed by acetylcholine (ACh). In the coronary arteries of 2K-1C rats, this ACh-induced relaxation depended on COX. The activation of TP receptors increased the production of PGI(2) in the coronary arteries of 2K-1C rats. The results demonstrated that increased COX signaling in the coronary arteries of 2K-1C rats mediated the low levels of CPP, the contraction induced by the activation of TP receptors, and the endothelium-dependent relaxation. The vasodilator PGI(2) seemed to be the major product. Conclusion: Activation of TP receptors increases production of PGI(2) in coronary arteries of 2K-1C rats. (AU)

• FAPESP's process: 15/00658-1 - New functional aspects of eicosanoids
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 15/17080-2 - Effects of the stretching on the vasoconstriction modulated by the endothelium in renal hypertensive rat aorta and coronary arteries
• Grantee: Lusiane Maria Bendhack
• Support Opportunities: Regular Research Grants