NDLI: Heme oxygenase induction attenuates afferent arteriolar autoregulatory responses.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Botros, Fady T. Prieto-Carrasquero, Minolfa C. Martin, Victoria L. Navar, L. Gabriel
Description	Country affiliation: United States Author Affiliation: Botros FT ( Department of Physiology, Hypertension and Renal Center, Tulane University Health Sciences Center, 1430 Tulane Ave., SL39, New Orleans, LA 70112, USA. fbotros@tulane.edu)
Abstract	Heme oxygenases (HO-1, HO-2) catalyze conversion of heme to iron, carbon monoxide (CO), and biliverdin/bilirubin. We studied the effects of renal HO-1 induction on afferent arteriole (Aff-Art) autoregulatory responses to increases in renal perfusion pressure (RPP). Rats were treated with hemin and SnCl2 to induce HO-1, and Aff-Art autoregulatory responses were evaluated using the rat blood-perfused juxtamedullary nephron preparation. Renal HO-1 expression was significantly increased in hemin- and SnCl2-treated rats, while HO-2 was not altered. Aff-Art autoregulatory constrictor responses to increases in RPP from 100 to 150 mmHg were attenuated in hemin- and SnCl2-treated rats compared with control rats (+1.1+/-3.3, n=9 and +4.4+/-5.3, n=9 vs. -14.2+/-1.5%, n=10, respectively) (P<0.05). Acute HO inhibition with chromium mesoporphyrin (CrMP; 15 micromol/l) restored Aff-Art autoregulatory responses in hemin- and SnCl2-treated rats. Superfusing Aff-Arts from control rats with 100 micromol/l biliverdin did not alter autoregulatory responses; however, superfusion with 1 mmol/l CO significantly attenuated autoregulatory responses to increases in RPP from 100 to 150 mmHg (+3.3+/-5.4 vs. -16.6+/-3.8%, n=6) (P<0.05). Acute soluble guanylate cyclase inhibition with 10 micromol/l ODQ restored Aff-Art autoregulatory responses in hemin-treated rats. Immunohistochemistry shows HO-2 to be expressed mainly in epithelial cells with weak staining in proximal tubules, interlobular arteries, and Aff-Arts. In hemin- and SnCl2-treated rats, HO-1 was induced in tubular epithelial cells but not interlobular arteries and Aff-Arts. We conclude that induction of renal HO-1 attenuates Aff-Art constrictor responses to increases in RPP via increasing CO production from tubular epithelial cells, suggesting that an augmented HO system in pathophysiological conditions modulates renal autoregulation.
File Format	HTM / HTML
ISSN	1931857X
e-ISSN	15221466
DOI	10.1152/ajprenal.90377.2008
Journal	AJP: Renal Physiology
Issue Number	4
Volume Number	295
Language	English
Publisher	American Physiological Society
Publisher Date	2008-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Blood Pressure Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Enzyme Inhibitors Arterioles Carbon Monoxide Heme Oxygenase (decyclizing) Biliverdine Homeostasis Antagonists & Inhibitors Vasodilation Discipline Physiology Physiology Vasoconstriction Rats, Sprague-dawley Discipline Nephrology Pharmacology Metabolism Drug Effects Animals Hemin Tin Compounds Guanylate Cyclase Renal Circulation Receptors, Cytoplasmic And Nuclear
Content Type	Text
Resource Type	Article
Subject	Physiology Urology

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