Vasoconstrictor Effects of Trace Amine-Associated Receptor Agonists in the Isolated Perfused Rat Kidney

Introduction: Endogenous trace amines such as tryptamine and 3-iodothyronamine (T1AM) are present in mammalian tissues at very low concentrations. They produce their actions by activating surface G proteincoupled receptors known as trace amine-associated receptors (TAARs). Objective: The study was designed to investigate the possible vasoconstrictor effects of tryptamine, T1AM, and the selective TAAR1 agonist RO5263397 in isolated perfused rat kidney. Methods: Renal vascular reactivity experiment using male Wistar Kyoto (WKY, n = 76) and spontaneously hypertensive rats (SHRs, n = 81) were used in this study. Results: Tryptamine (1011 106 mole), T1AM (1011 106 mole), and RO5263397 (1011 106 mole) increased perfusion pressure in preparations from WKY rats and SHRs in a dosedependent manner. EPPTB, a selective TAAR1 antagonist (10-6 M), significantly (p < 0.05) reduced agonistinduced increase in perfusion pressure in both WKY rats and SHRs, suggesting a role for TAAR1 activation in these responses. The vasoconstrictor responses in both groups were significantly reduced by L-type dihydropyridine calcium channel blocker, Rho-kinase, and protein kinase C (PKC) inhibitors suggesting the involvement of extracellular calcium and enhanced calcium sensitization. Reactive oxygen species (ROS) scavenger TEMPO significantly inhibited the agonistinduced increase in perfusion pressure in preparations from SHRs but not WKY. Conclusion: The TAARs enhanced agonist-induced increase in perfusion causing vasoconstriction in the kidney involves the influx of extracellular calcium, increased calcium sensitization, and ROS in SHRs animals only.