Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UMLS:C0920646 (
renal ischemia
)
2,515
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Renal vasoconstriction, an early manifestation of ischemic acute kidney injury (AKI), results in renal hypoperfusion and a rapid decline in kidney function. The pathophysiological mechanisms that underlie ischemia-reperfusion (IR)-induced renal insufficiency are poorly understood, but possibilities include alterations in ion channel-dependent renal vasoregulation. In the present study, we show that pharmacological activation of
TRPV4
channels constricted preglomerular microvessels and elicited renal hypoperfusion in neonatal pigs. Bilateral
renal ischemia
followed by short-term reperfusion increased
TRPV4
protein expression in resistance size renal vessels and
TRPV4
-dependent cation currents in renal vascular smooth muscle cells (SMCs). Selective
TRPV4
channel blockers attenuated IR-induced reduction in total renal blood flow (RBF), cortical perfusion, and glomerular filtration rate (GFR).
TRPV4
inhibition also diminished renal IR-induced increase in AKI biomarkers. Furthermore, the level of angiotensin II (Ang II) was higher in the urine of IR- compared with sham-operated neonatal pigs. IR did not alter renal vascular expression of Ang II type 1 (AT
1
) receptors. However, losartan, a selective AT
1
receptor antagonist, ameliorated IR-induced renal insufficiency in the pigs. Blockade of
TRPV4
channels attenuated Ang II-evoked receptor-operated Ca
2+
entry and constriction in preglomerular microvessels.
TRPV4
inhibition also blunted Ang II-induced increase in renal vascular resistance (RVR) and hypoperfusion in the pigs. Together, our data suggest that SMC
TRPV4
-mediated renal vasoconstriction and the ensuing increase in RVR contribute to early hypoperfusion and renal insufficiency elicited by renal IR in neonatal pigs. We propose that multimodal signaling by renal vascular SMC
TRPV4
channels controls neonatal renal microcirculation in health and disease.
...
PMID:Pharmacological inhibition of TRPV4 channels protects against ischemia-reperfusion-induced renal insufficiency in neonatal pigs. 3098 31
