From the Hypertension and Vascular Research Division, Henry Ford
Hospital, Detroit, Mich.
Abstract—Chronic two-kidney, one
clip (2K1C) renovascular hypertension is characterized by a largely
angiotensin-independent elevated blood pressure (BP). We
hypothesized that the long-term effect of hypertension would compromise
endothelium-derived nitric oxide (NO) and diminish its
influence in controlling renal perfusion. We determined the influence
of endothelium-derived NO on renal
hemodynamics and the angiotensin-NO
interaction regulation of renal perfusion in rats with chronic 2K1C
hypertension. Renal blood flow (RBF) was measured by radioactive
microspheres in rats with either early-phase (4 weeks after
clipping, n=7) or chronic-phase (13 to 16 weeks after clipping, n=7)
2K1C hypertension. The systemic and renal response to NO synthesis
inhibition was determined with 10 mg/kg body wt
N
© 1998 American Heart Association, Inc.
Scientific Contributions
Influence of Nitric Oxide in the Chronic Phase of Two-Kidney, One Clip Renovascular Hypertension
-nitro-L-arginine methyl
ester (L-NAME). In rats with early-phase 2K1C hypertension, BP was
149±3 mm Hg, which increased by 42±3 mm Hg with L-NAME
(P<.001). L-NAME decreased RBF by 20%
(P<.02) and 17% (P<.005) and increased
renal vascular resistance (RVR) by 58% (P<.005) and
62% (P<.02) in the nonclipped and clipped kidneys,
respectively. In rats with chronic 2K1C hypertension, BP was
166±3 mm Hg, and L-NAME increased this by 35±6 mm Hg
(P<.001). In the nonclipped and clipped kidneys of
chronic 2K1C hypertensive rats, L-NAME decreased RBF by 20%
(P<.01) and 17% (P<.01) and increased
RVR by 51% (P<.005) and 60% (P<.02),
respectively. There were no differences in L-NAME–induced changes
between early- and chronic-phase 2K1C hypertensive rats. Next, we
treated seven chronic-phase 2K1C hypertensive rats with 10 mg/kg body
wt losartan, which reduced BP by only 7.7%
(P<.005). After losartan, L-NAME increased BP
by 41±3 mm Hg (P<.001), decreased RBF to the
nonclipped kidney by 44% (P<.05), and increased RVR by
110% (P<.005); the decrease in RBF was significantly
greater compared with untreated chronic-phase controls
(P<.05). In the clipped kidney, L-NAME decreased RBF by
26% (P<.05) and increased RVR by 76%
(P <.05). Thus, angiotensin blockade did
not attenuate the systemic or renal vasoconstriction to L-NAME. Our
results suggest that in both early and chronic phases of 2K1C
hypertension, NO contributes significant dilator tone to buffer the
hypertension and maintains perfusion of both kidneys by
counterbalancing angiotensin-independent
vasoconstriction.
Key Words: renovascular hypertension • nitric oxide • angiotensin • blood pressure • renal perfusion
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