TY - JOUR
T1 - Suppressed impact of nitric oxide on renal arteriolar function in rats with chronic heart failure
AU - Ikenaga, Hideki
AU - Ishii, Naohito
AU - Didion, Sean P.
AU - Zhang, Kun
AU - Cornish, Kurtis G.
AU - Patel, Kaushik P.
AU - Mayhan, William G.
AU - Carmines, Pamela K.
PY - 1999/1
Y1 - 1999/1
N2 - We performed experiments to test the hypothesis that experimental heart failure (HF) is associated with altered nitric oxide (NO)-dependent influences on the renal microvasculature, including diminished modulation of constrictor responses to ANG II. Eight to ten weeks after inducing HF in rats by coronary artery ligation, we administered enalaprilat to suppress ANG II synthesis and studied renal arteriolar function using the in vitro blood- perfused juxtamedullary nephron technique. In kidneys from sham-operated rats, NO synthase inhibition [100 μM N(omega)-nitro-L-arginine (L-NNA)] reduced afferent arteriolar diameter by 4.1 ± 0.6 μm and enhanced ANG II responsiveness (10 nM ANG II decreased afferent diameter by 10.1 ± 1.4 μm before and 12.8 ± 1.6 μm during L-NNA treatment; P < 0.05). In kidneys from HF rats, L-NNA did not alter afferent arteriolar baseline diameter or ANG II responsiveness (10 nM ANG II decreased diameter by 12.5 ± 1.5 μm before and 12.5 ± 2.3 μm during L-NNA). The effects of L-NNA on efferent arteriolar function were also abated in HF rats. In renal cortex of HF rats, NO synthase activity was decreased by 63% and superoxide dismutase activity was diminished by 39% relative to tissue from sham-operated rats. Urinary nitrate/nitrite excretion was also reduced in HF rats. Thus both diminished synthesis and augmented degradation are likely to contribute to a decreased renal microvascular impact of endogenous NO during chronic HF, the consequences of which include loss of NO-dependent modulation of ANG II- induced vasoconstriction.
AB - We performed experiments to test the hypothesis that experimental heart failure (HF) is associated with altered nitric oxide (NO)-dependent influences on the renal microvasculature, including diminished modulation of constrictor responses to ANG II. Eight to ten weeks after inducing HF in rats by coronary artery ligation, we administered enalaprilat to suppress ANG II synthesis and studied renal arteriolar function using the in vitro blood- perfused juxtamedullary nephron technique. In kidneys from sham-operated rats, NO synthase inhibition [100 μM N(omega)-nitro-L-arginine (L-NNA)] reduced afferent arteriolar diameter by 4.1 ± 0.6 μm and enhanced ANG II responsiveness (10 nM ANG II decreased afferent diameter by 10.1 ± 1.4 μm before and 12.8 ± 1.6 μm during L-NNA treatment; P < 0.05). In kidneys from HF rats, L-NNA did not alter afferent arteriolar baseline diameter or ANG II responsiveness (10 nM ANG II decreased diameter by 12.5 ± 1.5 μm before and 12.5 ± 2.3 μm during L-NNA). The effects of L-NNA on efferent arteriolar function were also abated in HF rats. In renal cortex of HF rats, NO synthase activity was decreased by 63% and superoxide dismutase activity was diminished by 39% relative to tissue from sham-operated rats. Urinary nitrate/nitrite excretion was also reduced in HF rats. Thus both diminished synthesis and augmented degradation are likely to contribute to a decreased renal microvascular impact of endogenous NO during chronic HF, the consequences of which include loss of NO-dependent modulation of ANG II- induced vasoconstriction.
KW - Angiotensin II
KW - Myocardial infarction
KW - Nitric oxide synthase
KW - Renal microvasculature
KW - Superoxide dismutase
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U2 - 10.1152/ajprenal.1999.276.1.f79
DO - 10.1152/ajprenal.1999.276.1.f79
M3 - Article
C2 - 9887083
AN - SCOPUS:0032891468
VL - 276
SP - F79-F87
JO - American journal of physiology. Renal physiology
JF - American journal of physiology. Renal physiology
SN - 0363-6127
IS - 1 45-1
ER -