Ablation of TRPV1 Abolishes Endothelin Induced Increases in Afferent Renal Nerve Activity: Mechanisms and Functional Significance

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 54; no. 6; pp. 1298 - 1305
• Main Authors: Xie, Chaoqin, Wang, Donna H.
• Format: Journal Article
• Language: English
• Published: 26.10.2009
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.109.132167

Endothelin 1 (ET-1) and its receptors, ETA and ETB, play an important role in regulating renal function and blood pressure, and these components are expressed in sensory nerves. Activation of transient receptor potential vanilloid 1 (TRPV1) channels expressed in sensory nerves innervating the renal pelvis enhances afferent renal nerve activity (ARNA), diuresis, and natriuresis. We test the hypothesis that ET1 increases ARNA via activation of ETB, whereas ETA counter-balances ETB in wild type (WT) but not TRPV1-null mutant (TRPV−/−) mice. ET-1 alone or with BQ123, an ETA antagonist, perfused into the left renal pelvis increased ipsilaterel ARNA in WT but not TRPV−/− mice, and ARNA increases were greater in the latter. [Ala1, 3,11,15]-endothelin 1 (4 Ala-ET-1), an ETB agonist, increased ARNA that was greater than that induced by ET-1 in WT mice only. 4 Ala-ET-1-induced increases in ARNA were abolished by chelerythrine (CHE), a protein kinase C (PKC) inhibitor, but not by H89, a protein kinase A (PKA) inhibitor. Neither CHE, H89, nor BQ788, an ETB antagonist, affected ARNA triggered by capsaicin (CAP) in WT mice. Substance P (SP) release from the renal pelvis was increased by 4 Ala-ET-1 in WT mice only, and the increase was abolished by CHE but not by H89. Neither CHE, H89, nor BQ788 affected CAP-induced SP release. Our data show that ET1 increases ARNA via activation of ETB whereas ETA counter-balances ETB in WT but not TRPV−/− mice, suggesting that TRPV1 mediates ETB-dependent increases in ARNA, diuresis, and natriuresis via possibly the PKC pathway.