The role of haem oxygenase in renal vascular reactivity in normotensive and hypertensive rats

Objective To evaluate the contribution of the haem oxygenase-carbon monoxid e (CO) system to renal vascular tone in normotensive Wistar rats and in the stroke-prone spontaneously hypertensive rats (SHR-SPs). Methods An isolated perfused rat kidney preparation was used in which perfu sion pressure/phenylephrine dose-vasoconstrictor responses were generated, Haemin was given 24 h previously, to induce haem oxygenase-1 (HO-1), and L- NAME (N-omega -nitro-L-arginine methyl ester) was given to block nitric oxi de (NO) production. Results Haemin pretreatment attenuated the phenylephrine-induced rise in pe rfusion pressure (P < 0.05) but L-NAME had no effect on the magnitude of th e renal vasoconstrictor responses to phenylephrine. This suggested that the effect of haemin incubation on renovascular responses did not involve NO p roduction. Pretreatment of the rats with the haem oxygenase inhibitor, tin protoporphyrin IX (SnPP-IX) had no effect on either the basal tone or the p henylephrine-induced contractions in the renal vasculature. By contrast, th e renovascular responses to phenylephrine in haemin-treated animals were re stored following the co-administration of SnPP-IX, Haemin administration in the SHR-SPs; caused a significantly greater reduction in the renovascular responses to phenylephrine compared to those in the normotensive animals (P < 0.05). Conclusions Following induction of NO-1, the NO-CO system plays an importan t role in the regulation of renal responses to an adrenergically induced va soconstrictor challenge. Moreover, the renal vascular bed of hypertensive a nimals exhibited a greater propensity to upregulate the NO-CO system, which may provide an important counteractive role against the elevation of blood pressure in hypertension. (C) 2001 Lippincott Williams & Wilkins.