Soluble guanylate cyclase (sGC) plays an important role in
nitric oxide (NO)-mediated regulation of vascular tone; however, NO bioavailability is often reduced in diseased blood vessels. Accumulating evidence suggests that a shift of sGC from the NO-sensitive form to the NO-insensitive form could be an underlying cause contributing to this reduction. Herein, we investigated the impact of
renovascular hypertension on NO-sensitive and NO-insensitive sGC-mediated relaxation in rat aortas.
Renovascular hypertension was induced by partially clipping the left renal artery (2-kidneys, 1-
clip; 2K1C) for 10 weeks. Systolic, diastolic, and mean arterial pressures were significantly increased in the 2K1C group when compared with the
sham group. In addition, plasma
thiobarbituric acid reactive substances and aortic
superoxide generation were significantly enhanced in the 2K1C group when compared with those in the
sham group. The
vasorelaxant response of isolated aortas to the sGC stimulator
BAY 41-2272 (NO-sensitive sGC agonist) was comparable between the
sham and 2K1C groups. Likewise, the sGC activator
BAY 60-2770 (NO-insensitive sGC agonist)-induced relaxation did not differ between the
sham and 2K1C groups. In addition, the cGMP mimetic 8-Br-cGMP (
protein kinase G agonist) induced similar relaxation in both groups. Furthermore, there were no differences in BAY 41-2272-stimulated and BAY 60-2770-stimulated cGMP generation between the groups. These findings suggest that the balance between NO-sensitive and NO-insensitive forms of sGC is maintained during
renovascular hypertension. Therefore, sGC might not be responsible for the reduced NO bioavailability observed during
renovascular hypertension.