| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI, USA
* To whom correspondence should be addressed. E-mail: jgarvin1{at}hfhs.org.
Endothelin-1 (ET-1) acutely inhibits NaCl reabsorption by the thick ascending limb (THAL) by activating the ETB receptor, stimulating endothelial nitric oxide synthase (eNOS) and releasing nitric oxide (NO). In non-renal tissue, chronic exposure to ET-1 stimulates eNOS expression via the ETB receptor and activation of phosphatidylinositol 3-kinase (PI3K). We hypothesized that ET-1 increases eNOS expression in the THAL by binding to ETB receptors and stimulating PI3K. In primary cultures of medullary THALs treated for 24 hr, eNOS expression increased by 36±18% with 0.01nM ET-1, 123±30% with 0.1nM (p<0.05; n = 5) and 71±30% with 1nM, whereas 10nM had no effect. BQ788, a selective ETB receptor antagonist completely blocked stimulation of eNOS expression caused by 0.1nM ET-1 (12±25% vs. 120±40% for ET-1 alone; p<0.05; n = 5). BQ123, a selective ETA receptor antagonist, did not affect the increase in eNOS caused by 0.1nM ET-1. 0.1µM Sarafotoxin c (S6c), a selective ETB receptor agonist, increased eNOS expression by 77±30% (p<0.05; n = 6). 0.01µM wortmannin, a PI3K inhibitor, completely blocked the stimulatory effect of 0.1µM S6c (77±30% vs. -28±9%; p<0.05; n = 6). To test whether the increase in eNOS expression heightens activity, we measured NO release in response to simultaneous treatment with L-arginine, ionomycin and clonidine using a NO-sensitive electrode. NO release by control cells was 337±61 pAmps and 690±126 pAmps in ET-1 treated cells (p<0.05; n = 5). Taken together, these data suggest that ET-1 stimulates THAL eNOS, activating ETB receptors and PI3K and thereby increasing NO production.
This article has been cited by other articles:
|
|
 |
|
  M. P. Schneider, Y. Ge, D. M. Pollock, J. S. Pollock, and D. E. Kohan Collecting Duct-Derived Endothelin Regulates Arterial Pressure and Na Excretion via Nitric Oxide Hypertension, June 1, 2008; 51(6): 1605 - 1610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Strait, P. K. Stricklett, J. L. Kohan, M. B. Miller, and D. E. Kohan Calcium regulation of endothelin-1 synthesis in rat inner medullary collecting duct Am J Physiol Renal Physiol, August 1, 2007; 293(2): F601 - F606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Herrera and J. L. Garvin Novel role of AQP-1 in NO-dependent vasorelaxation Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1443 - F1451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tsuruoka, S. Watanabe, J. M. Purkerson, A. Fujimura, and G. J. Schwartz Endothelin and nitric oxide mediate adaptation of the cortical collecting duct to metabolic acidosis Am J Physiol Renal Physiol, October 1, 2006; 291(4): F866 - F873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Herrera, P. A. Ortiz, and J. L. Garvin Regulation of thick ascending limb transport: role of nitric oxide Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1279 - F1284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Stricklett, A. K. Hughes, and D. E. Kohan Endothelin-1 stimulates NO production and inhibits cAMP accumulation in rat inner medullary collecting duct through independent pathways Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1315 - F1319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Dhaun, J. Goddard, and DavidJ. Webb The Endothelin System and Its Antagonism in Chronic Kidney Disease J. Am. Soc. Nephrol., April 1, 2006; 17(4): 943 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Herrera, G. Silva, and J. L. Garvin A High-Salt Diet Dissociates NO Synthase-3 Expression and NO Production by the Thick Ascending Limb Hypertension, January 1, 2006; 47(1): 95 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Herrera and J. L. Garvin Recent Advances in the Regulation of Nitric Oxide in the Kidney Hypertension, June 1, 2005; 45(6): 1062 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Garvin and M. Herrera Physiological actions of renal collecting duct endothelin Am J Physiol Renal Physiol, May 1, 2005; 288(5): F910 - F911. [Full Text] [PDF]
|
|
|
|
|
|
M. Herrera and J. L. Garvin A high-salt diet stimulates thick ascending limb eNOS expression by raising medullary osmolality and increasing release of endothelin-1 Am J Physiol Renal Physiol, January 1, 2005; 288(1): F58 - F64. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
