Blood flow-dependent changes in renal interstitial guanosine 3',5'-cyclic monophosphate in rabbits.
We examined responses of renal interstitial guanosine 3',5'-cyclic monophosphate (cGMP) to changes in renal perfusion pressure (RPP) within and below the range of renal blood flow (RBF) autoregulation. A microdialysis method was used to monitor renal cortical and medullary interstitial cGMP levels in anesthetized rabbits. RPP was reduced in two steps: from ambient pressure (89 +/- 3 mmHg) to 70 +/- 2 mmHg (step 1) and then to 48 +/- 3 mmHg (step 2). RBF was maintained in step 1 but was significantly decreased in step 2 from 2.94 +/- 0.23 to 1.47 +/- 0.08 ml x min(-1) x g(-1). Basal interstitial concentrations of cGMP were significantly lower in the cortex than in the medulla (12.1 +/- 1.4 and 19.9 +/- 0.4 nmol/l, respectively). Cortical and medullary cGMP did not change in step 1 but were significantly decreased in step 2, with significantly less reduction in cGMP concentrations in the medulla than in the cortex (-25 +/- 3 and -44 +/- 3%, respectively). Over this pressure range, changes in cortical and medullary cGMP were highly correlated with changes in RBF (r = 0.94, P < 0.005 for cortex; r = 0.82, P < 0.01 for medulla). Renal interstitial nitrate/nitrite was not changed in step 1 but was significantly decreased in step 2 (-38 +/- 2% in cortex and -20 +/- 2% in medulla). Nitric oxide synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg bolus, 50 mg x kg(-1) x h(-1) i.v. infusion) significantly decreased RBF (by -46 +/- 4%) and interstitial concentrations of cGMP (-27 +/- 4% in cortex and -22 +/- 4% in medulla, respectively). During L-NAME treatment, renal interstitial concentrations of cGMP in the cortex and medulla were similarly not altered in step 1. However, L-NAME significantly attenuated cGMP responses to a reduction in RPP in step 2. These results indicate that acute changes in RBF result in alterations in nitric oxide-dependent renal interstitial cGMP levels, with differential effects in the medulla compared with the cortex.
Nishiyama
Akira
A
Department of Pharmacology, Kagawa Medical University, Kagawa 761-0793, Japan. yakuri@kms.ac.jp
Kimura
Shoji
S
Fukui
Toshiki
T
Rahman
Matlubur
M
Yoneyama
Hirohito
H
Kosaka
Hiroaki
H
Abe
Youichi
Y
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007672:Kidney Cortex / Q000098:blood supply / Q000378:metabolism*; D007679:Kidney Medulla / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D012079:Renal Circulation / Q000502:physiology*
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester