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 protein-coupled 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 dose-dependent manner. EPPTB, a selective TAAR1 antagonist (10⁻⁶ M), significantly (p < 0.05) reduced agonist-induced 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 agonist-induced 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.