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Citations to this article

Potentiation of tubuloglomerular feedback in the rat by thromboxane mimetic. Role of macula densa.
W J Welch, C S Wilcox
W J Welch, C S Wilcox
Published June 1, 1992
Citation Information: J Clin Invest. 1992;89(6):1857-1865. https://doi.org/10.1172/JCI115790.
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Research Article Article has an altmetric score of 5

Potentiation of tubuloglomerular feedback in the rat by thromboxane mimetic. Role of macula densa.

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Abstract

Because endogenous thromboxane A2 (TXA2) potentiates the tubuloglomerular feedback response (TGF), we studied the mechanism of action of TXA2 by using a stable TXA2/prostaglandin (PG) H2 mimetic, U-46,619. Intravenous infusion of U-46,619 at 100 ng.kg-1.min-1 reduced the GFR and the single-nephron (SN)GFR measured from the distal tubule (macula densa function intact), whereas the SNGFR measured from the proximal tubule (macula densa function interrupted) was not changed consistently. 10-100-fold higher rates of infusion of U-46,619 were required to raise blood pressure or femoral vascular resistance. The regulation of glomerular capillary pressure (PGC) by TGF was assessed in anesthetized rats from changes in proximal stop flow pressure (PSF) and/or SNGFR during perfusion of the loop of Henle (LH) with artificial tubular fluid (ATF). Orthograde loop perfusion and retrograde perfusion of U-46,619 into the macula densa segment reduced PSF. Responses to luminal U-46,619 were blunted by a TXA2-PGH2 receptor antagonist. Orthograde loop perfusions with luminal U-46,619 increased net Cl absorption, whereas coperfusion with furosemide (10(-4) M) blunted the response to U-46,619 by 68%. These data indicated that the luminal U-46,619 might increase the signal for TGF activation by increasing Cl reabsorption in macula densa cells. However, since 80 +/- 4% of [3H]U-46,619 perfused via the LH was reabsorbed peritubular capillaries (PTC) were perfused with U-46,619 to test additional extra-luminal actions. PTC perfusion with U-46,619 again increased TGF by reducing PSF selectively only while macula densa function was intact during perfusion of the LH with ATF. Conclusions: (a) TGF is potentiated by U-46,619 given systematically, via the lumen of the LH by orthograde or retrograde perfusions or via the PTC; (b) at the lower doses tested, reduction of PGC and SNGFR by U-46,619 depends on tubular fluid delivery and reabsorption by the macula densa; (c) potentiation of TGF by U-46,619 entails preglomerular vasoconstriction which may be elicited in part by an increased signal due to increased net chloride reabsorption in the LH and presumably macula densa cells and by an increased sensitivity of the arteriole to macula densa-derived signals; (d) activation of TGF may contribute to the selective vasoconstriction of the renal vascular bed by low doses of U-46,619.

Authors

W J Welch, C S Wilcox

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Total citations by year

Year: 2022 2020 2018 2015 2014 2013 2012 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1995 1994 1992 Total
Citations: 1 1 1 2 1 2 1 4 3 1 1 3 3 2 4 2 3 7 3 6 6 2 1 1 61
Citation information
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Citations to this article in year 2008 (1)

Title and authors Publication Year
Microcirculation
K Ley
Microcirculation 2008

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