Angiotensin II causes renal injury through hemodynamic and other effects, and pressor doses of angiotensin 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 angiotensin II, and the role of HO activity in influencing these effects. Under euvolemic conditions, angiotensin II increased arterial pressure and renal vascular resistance. Angiotensin II did not induce oxidative stress, inflammation/injury-related gene expression, or proteinuria, and did not alter extrarenal vascular reactivity. At these doses angiotensin II failed to increase HO-1 or HO-2 mRNA expression, or HO activity. Inhibiting HO activity in angiotensin II-treated rats by tin mesoporphyrin (SnMP) 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; SnMP did not alter vasorelaxation of mesenteric resistor vessels. We conclude that, in this model, renal vasoconstriction occurs without the recognized adverse effects of angiotensin II on GFR, renal blood flow, oxidative stress, vascular reactivity, proteinuria, and injury-related gene expression; renal HO activity is essential in preserving perfusion of the angiotensin II-exposed kidney. These findings represent an uncommon example wherein function of a "stressed" organ (by angiotensin 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 angiotensin II levels, "ineffective" renal perfusion, and susceptibility to acute kidney injury.
- angiotensin II
- renal hemodynamics
- heme oxygenase
- tin mesoporphyrin
- Copyright © 2010, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology