Heme oxygenase induction attenuates afferent arteriolar autoregulatory responses.
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.
Botros
Fady T
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
Prieto-Carrasquero
Minolfa C
MC
Martin
Victoria L
VL
Navar
L Gabriel
LG
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001664:Biliverdine / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D002248:Carbon Monoxide / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D000071756:Soluble Guanylyl Cyclase; D017971:Tin Compounds / Q000378:metabolism / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D017971:Tin Compounds; C023599:stannous chloride; D006427:Hemin; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C105245:heme oxygenase-2; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D001664:Biliverdine