The cytochrome P-450 inhibitor cobalt chloride prevents inhibition of renal Na,K-ATPase and redistribution of apical NHE-3 during acute hypertension.

Journal of the American Society of Nephrology : JASN
Y B ZhangA A McDonough

Abstract

Acute systolic arterial hypertension provokes a rapid decrease in proximal tubule sodium reabsorption and diuresis associated with inhibition of renal cortex Na,K-ATPase activity and redistribution of apical membrane Na/H exchanger (NHE-3) to heavier density membranes containing markers of intermicrovillar cleft and endosomes. Because cytochrome P-450-dependent arachidonate metabolites participate in the regulation of renal sodium transport and BP, this study tested the hypothesis that these renal responses to acute hypertension would be prevented if cytochrome P-450 metabolism were inhibited by cobalt chloride (CoCl2). Four groups of rats (n = 4 to 5) were studied: (1) sham-operated; (2) 50 mg of CoCl2/kg subcutaneously for 2 d; (3) acute hypertension by constricting arteries for 5 min; and (4) acute hypertension after CoCl2 treatment as in group 3. Renal cortex was analyzed after sorbitol density gradient fractionation. CoCl2 treatment alone did not significantly affect the rate of urine output, endogenous lithium clearance (an inverse measure of proximal tubule sodium reabsorption), maximal activity of Na,K-ATPase, or subcellular distribution of NHE-3-containing membranes. In non-CoCl2-treated animals, acute hypertension pro...Continue Reading

Citations

Apr 11, 2000·Current Opinion in Nephrology and Hypertension·C E Magyar, A A McDonough
Nov 9, 2000·Clinical and Experimental Pharmacology & Physiology·R J RomanM Alonso-Galicia
Nov 25, 2003·Prostaglandins & Other Lipid Mediators·David SacerdotiJohn C McGiff
Mar 20, 2004·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Elisabete A Dos SantosRichard J Roman
Jun 19, 2004·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Patrick K K LeongAlicia A McDonough
Apr 28, 2005·Clinical and Experimental Pharmacology & Physiology·Roger G EvansGabriela A Eppel
Aug 12, 2005·American Journal of Physiology. Renal Physiology·John D Imig
May 12, 2006·Journal of the American Society of Nephrology : JASN·Wisam SelbiAled O Phillips
Aug 5, 2008·Wiener medizinische Wochenschrift·Gert Mayer
Jan 16, 2009·American Journal of Physiology. Renal Physiology·Donna H LeeAlicia A McDonough
May 24, 2003·Annals of the New York Academy of Sciences·Alicia A McDonoughLi E Yang
Jan 29, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Alicia A McDonough
Apr 29, 2010·Current Hypertension Reports·Paul M O'Connor, Allen W Cowley
Oct 12, 2010·Journal of Cardiovascular Pharmacology·Jan M WilliamsRichard J Roman

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