Activation of Renal Vascular Smooth Muscle TRPV4 Channels by 5-hydroxytryptamine Impairs Kidney Function in Neonatal Pigs

Overview

Journal Microvasc Res

Specialty Cardiology & Vascular Diseases

Date 2023 Mar 8

PMID 36889668

Authors

Jeremiah M Afolabi

Olugbenga S Michael

Olufunke O Falayi

Praghalathan Kanthakumar

Pratheesh D Mankuzhy

Hitesh Soni

Adebowale Adebiyi

Affiliations

Soon will be listed here.

Abstract

Control of microvascular reactivity by 5-hydroxytryptamine (5-HT; serotonin) is complex and may depend on vascular bed type and 5-HT receptors. 5-HT receptors consist of seven families (5-HT-5-HT), with 5-HT predominantly mediating renal vasoconstriction. Cyclooxygenase (COX) and smooth muscle intracellular Ca levels ([Ca]) have been implicated in 5-HT-induced vascular reactivity. Although 5-HT receptor expression and circulating 5-HT levels are known to be dependent on postnatal age, control of neonatal renal microvascular function by 5-HT is unclear. In the present study, we demonstrate that 5-HT stimulated human TRPV4 transiently expressed in Chinese hamster ovary cells. 5-HT is the predominant 5-HT receptor subtype in freshly isolated neonatal pig renal microvascular smooth muscle cells (SMCs). HC-067047 (HC), a selective TRPV4 blocker, attenuated cation currents induced by 5-HT in the SMCs. HC also inhibited the 5-HT-induced increase in renal microvascular [Ca] and constriction. Intrarenal artery infusion of 5-HT had minimal effects on systemic hemodynamics but reduced renal blood flow (RBF) and increased renal vascular resistance (RVR) in the pigs. Transdermal measurement of glomerular filtration rate (GFR) indicated that kidney infusion of 5-HT reduced GFR. HC and 5-HT receptor antagonist ritanserin attenuated 5-HT effects on RBF, RVR, and GFR. Moreover, the serum and urinary COX-1 and COX-2 levels in 5-HT-treated piglets were unchanged compared with the control. These data suggest that activation of renal microvascular SMC TRPV4 channels by 5-HT impairs kidney function in neonatal pigs independently of COX production.

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References

Delaney C, Gien J, Roe G, Isenberg N, Kailey J, Abman S . Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn. Am J Physiol Lung Cell Mol Physiol. 2013; 304(12):L894-901. PMC: 3680750. DOI: 10.1152/ajplung.00043.2013. View

Pepeu G, GIARMAN N . Serotonin in the developing mammal. J Gen Physiol. 1962; 45:575-83. PMC: 2195182. DOI: 10.1085/jgp.45.3.575. View

Pill J, Kloetzer H, Issaeva O, Kraenzlin B, Deus C, Kraemer U . Direct fluorometric analysis of a newly synthesised fluorescein-labelled marker for glomerular filtration rate. Anal Bioanal Chem. 2005; 382(1):59-64. DOI: 10.1007/s00216-005-3155-y. View

Chen X, Alessandri-Haber N, Levine J . Marked attenuation of inflammatory mediator-induced C-fiber sensitization for mechanical and hypotonic stimuli in TRPV4-/- mice. Mol Pain. 2007; 3:31. PMC: 2173885. DOI: 10.1186/1744-8069-3-31. View

Takahashi T, Hisa H, Satoh S . Serotonin-induced vasoconstriction in dog kidney. J Cardiovasc Pharmacol. 1992; 20(5):779-84. View

Watts S, Thompson J . Characterization of the contractile 5-hydroxytryptamine receptor in the renal artery of the normotensive rat. J Pharmacol Exp Ther. 2004; 309(1):165-72. DOI: 10.1124/jpet.103.062562. View

Willemen S, Che L, Dewilde S, Van Hauwaert M, De Vos M, Huygelen V . Enteric and serological distribution of serotonin and its precursor tryptophan in perinatal low and normal weight piglets. Animal. 2014; 8(5):792-9. DOI: 10.1017/S1751731114000317. View

VAN ARMAN C . The antidiuretic effect of 5-hydroxytryptamine in the rat as influenced by dibenamine. Arch Int Pharmacodyn Ther. 1956; 108(3-4):356-65. View

Ratz P, Flaim S . Acetylcholine- and 5-hydroxytryptamine-stimulated contraction and calcium uptake in bovine coronary arteries: evidence for two populations of receptor-operated calcium channels. J Pharmacol Exp Ther. 1985; 234(3):641-7. View

10.

Palomo A, Martin P, Rebolledo A, Enrique N, Flores L, Milesi V . Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels. Biocell. 2012; 36(2):73-81. View

11.

Garcia-Alcocer G, Segura L, Garcia Pena M, Martinez-Torres A, Miledi R . Ontogenetic distribution of 5-HT2C, 5-HT5A, and 5-HT7 receptors in the rat hippocampus. Gene Expr. 2006; 13(1):53-7. PMC: 6032452. DOI: 10.3727/000000006783991935. View

12.

Carvalho J . Improved techniques for acute and chronic cannulation of renal artery in the rat. Kidney Int. 1982; 22(1):75-9. DOI: 10.1038/ki.1982.135. View

13.

Hill P, Dora K, Hughes A, Garland C . The involvement of intracellular Ca(2+) in 5-HT(1B/1D) receptor-mediated contraction of the rabbit isolated renal artery. Br J Pharmacol. 2000; 130(4):835-42. PMC: 1572141. DOI: 10.1038/sj.bjp.0703387. View

14.

Critchley L, Peng Z, Fok B, Lee A, Phillips R . Testing the reliability of a new ultrasonic cardiac output monitor, the USCOM, by using aortic flowprobes in anesthetized dogs. Anesth Analg. 2005; 100(3):748-753. DOI: 10.1213/01.ANE.0000144774.42408.05. View

15.

Filosa J, Yao X, Rath G . TRPV4 and the regulation of vascular tone. J Cardiovasc Pharmacol. 2012; 61(2):113-9. PMC: 3564998. DOI: 10.1097/FJC.0b013e318279ba42. View

16.

EMANUEL D, Scott J, Collins R, Haddy F . Local effect of serotonin on renal vascular resistance and urine flow rate. Am J Physiol. 1959; 196(5):1122-6. DOI: 10.1152/ajplegacy.1959.196.5.1122. View

17.

Dalton D, Feniuk W, Humphrey P . An investigation into the mechanisms of the cardiovascular effects of 5-hydroxytryptamine in conscious normotensive and DOCA-salt hypertensive rats. J Auton Pharmacol. 1986; 6(3):219-28. DOI: 10.1111/j.1474-8673.1986.tb00648.x. View

18.

Becker D, Blase C, Bereiter-Hahn J, Jendrach M . TRPV4 exhibits a functional role in cell-volume regulation. J Cell Sci. 2005; 118(Pt 11):2435-40. DOI: 10.1242/jcs.02372. View

19.

Xia Y, Yang X, Fu Z, Paudel O, Abramowitz J, Birnbaumer L . Classical transient receptor potential 1 and 6 contribute to hypoxic pulmonary hypertension through differential regulation of pulmonary vascular functions. Hypertension. 2013; 63(1):173-80. PMC: 4102175. DOI: 10.1161/HYPERTENSIONAHA.113.01902. View

20.

Soni H, Peixoto-Neves D, Matthews A, Adebiyi A . TRPV4 channels contribute to renal myogenic autoregulation in neonatal pigs. Am J Physiol Renal Physiol. 2017; 313(5):F1136-F1148. PMC: 5792157. DOI: 10.1152/ajprenal.00300.2017. View