title: Inhibition of heme oxygenase augments tubular sodium reabsorption.
abstract: Heme oxygenase (HO) catalyzes the degradation of heme to form iron, biliverdin, and carbon monoxide (CO). The vascular actions of CO include direct vasodilation of vascular smooth muscle and indirect vasoconstriction through inhibition of nitric oxide synthase (NOS). This study was performed to examine the effects in the kidney of inhibition of heme oxygenase alone or combined with NOS inhibition. Chromium mesoporphyrin (CrMP; 45 μmol/kg ip), a photostable HO inhibitor, was given to control rats and N(G)-nitro-l-arginine methyl ester (l-NAME)-treated hypertensive rats (50 mg·kg⁻¹·day⁻¹), 12 h, 4 days). In control animals, CrMP decreased CO levels, renal HO-1 levels, urine volume, and sodium excretion, but had no effect on arterial pressure, renal blood flow (RBF), plasma renin activity (PRA), or glomerular filtration rate (GFR). In l-NAME-treated hypertensive rats, CrMP decreased endogenous CO and renal HO-1 levels and had no effect on arterial pressure, RBF, or GFR but decreased sodium and water excretion in a similar manner to control animals. An increase in PRA was observed in untreated rats but not in l-NAME-infused rats, indicating that this effect is associated with an absent NO system. The results suggest that inhibition of HO promotes water and sodium excretion by a direct tubular action that is independent of renal hemodynamics or the NO system.
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, Univ. of Louisiana at Monroe, Monroe, LA 71201, USA. kjackson@ulm.edu
authors.forename: Keith E
authors.initials: KE
authors.lastname: Jackson
authors.forename: Debra W
authors.initials: DW
authors.lastname: Jackson
authors.forename: Syed
authors.initials: S
authors.lastname: Quadri
authors.forename: Marshall J
authors.initials: MJ
authors.lastname: Reitzell
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D002248:Carbon Monoxide; D012964:Sodium; D052250:Nitric Oxide Synthase Type III; D006419:Heme Oxygenase (Decyclizing); D019331:NG-Nitroarginine Methyl Ester