Heme oxygenase activity as a determinant of the renal hemodynamic response to low-dose ANG II

Karl A. Nath, Melissa C. Hernandez, Anthony J. Croatt, Zvonimir S. Katusic, Luis A. Juncos

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

ANG II causes renal injury through hemodynamic and other effects, and pressor doses of ANG II induce heme oxygenase-1 (HO-1) as a protective response. The present studies examined the hemodynamic effects of more clinically relevant, lower doses of ANG II and the role of HO activity in influencing these effects. Under euvolemic conditions, ANG II increased arterial pressure and renal vascular resistance. ANG II did not induce oxidative stress, inflammation/injury-related gene expression, or proteinuria and did not alter extrarenal vascular reactivity. At these doses, ANG II failed to increase HO-1 or HO-2 mRNA expression or HO activity. Inhibiting HO activity in ANG II-treated rats by tin mesoporphyrin further increased renal vascular resistances, decreased renal blood flow, and blunted the rise in arterial pressure without inducing oxidative stress or altering expression of selected vasoactive/injury/inflammation-related genes; tin mesoporphyrin did not alter vasorelaxation of mesenteric resistor vessels. We conclude that in this model renal vasoconstriction occurs without the recognized adverse effects of ANG II on glomerular filtration rate, renal blood flow, oxidative stress, vascular reactivity, proteinuria, and injury-related gene expression; renal HO activity is essential in preserving perfusion of the ANG II-exposed kidney. These findings represent an uncommon example wherein function of a stressed organ (by ANG II), but not that of the unstressed organ, requires intact renal HO activity, even when the imposed stress neither induces HO-1 nor HO activity. These findings may be germane to conditions attended by heightened ANG II levels, ineffective renal perfusion, and susceptibility to acute kidney injury.

Original languageEnglish (US)
Pages (from-to)R1183-R1191
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume299
Issue number5
DOIs
StatePublished - Nov 2010

Keywords

  • Ischemia
  • Tin mesoporphyrin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Heme oxygenase activity as a determinant of the renal hemodynamic response to low-dose ANG II'. Together they form a unique fingerprint.

  • Cite this