title: Chronic noradrenaline increases renal expression of NHE-3, NBC-1, BSC-1 and aquaporin-2.
abstract: 1. Because chronic activation of the renal sympathetic nervous system promotes sodium and water retention, it is conceivable that long-term exposure of the kidney to the sympathetic neurotransmitter noradrenaline upregulates the expression of key renal epithelial transport systems. 2. To test this hypothesis, we used immunoblotting of renal cortical and medullary tissue to investigate the abundance of major transport systems expressed along the renal tubule in response to long-term (15 days) infusions of noradrenaline (600 ng/min) in rats. 3. Mean arterial blood pressure and heart rate were significantly elevated in rats receiving chronic infusions of noradrenaline (128 +/- 10 mmHg and 492 +/- 16 b.p.m., respectively) compared with animals treated with saline only (89 +/- 3 mmHg and 376 +/- 14 b.p.m., respectively). 4. Chronic infusions of noradrenaline also increased the protein abundance of the cortical Na(+)/H(+) exchanger isoform 3 (NHE-3; 2.5-fold; P = 0.0142), the cortical sodium-bicarbonate cotransporter NBC-1 (2.5-fold; P = 0.0067), the bumetanide-sensitive sodium-potassium-chloride cotransporter BSC-1/NKCC2 in the inner stripe of outer medulla (threefold; P = 0.0020) and aquaporin-2 in the inner medulla (twofold; P = 0.0039). 5. In contrast, noradrenaline did not significantly affect expression of the thiazide-sensitive Na(+)-Cl(-) cotransporter in the cortex, Na(+)/K(+)-ATPase-alpha(1) in the cortex and inner stripe of the outer or inner medulla, the inwardly rectifying K(+) channel (ROMK-1) in the inner stripe of the outer medulla or aquaporin-1 in the cortex or inner medulla. Noradrenaline did significantly, but modestly (less than twofold), increase aquaporin-1 in the inner stripe of the outer medulla. 6. We conclude that noradrenaline-induced increases in the expression of NHE-3, NBC-1, BSC-1 and aquaporin-2 are likely to play an important role in the regulation of salt and water transport by noradrenaline in the kidney and may explain, at least in part, the altered renal sodium and water handling associated with overactivation of the sympathetic system.
authors.affiliation: Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219-3130, USA.
authors.forename: Prajakta A
authors.initials: PA
authors.lastname: Sonalker
authors.forename: Stevan P
authors.initials: SP
authors.lastname: Tofovic
authors.forename: Sheldon I
authors.initials: SI
authors.lastname: Bastacky
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Jackson
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000096:biosynthesis*; D001794:Blood Pressure / Q000187:drug effects; D004334:Drug Administration Schedule; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000096:biosynthesis; D049992:Sodium Chloride Symporters / Q000096:biosynthesis; D027982:Sodium-Bicarbonate Symporters / Q000096:biosynthesis*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis*; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis*; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis; D064466:Solute Carrier Family 12, Member 1; D013047:Specific Pathogen-Free Organisms; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C496025:Aqp2 protein, rat; D051399:Aquaporin 2; C510692:Kcnj1 protein, rat; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; C578716:Slc12a1 protein, rat; C422004:Slc4a4 protein, rat; C000613387:Slc9a3 protein, rat; D049992:Sodium Chloride Symporters; D027982:Sodium-Bicarbonate Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; C064415:thiazide receptor; D000254:Sodium-Potassium-Exchanging ATPase; D009638:Norepinephrine