The contribution of nitric oxide to diuretic and natriuretic effects of renal kinins in normotensive rats.
We have reported that diuresis and natriuresis due to increase in renal kinins induced by the neutral endopeptidase 24.11 (NEP) inhibitor were attenuated by nitric oxide (NO) synthase inhibitor. To further clarify the water-sodium excretory mechanism of renal kinins, we estimated NO2+NO3 (NOx) and cGMP in plasma and urine with and without a specific NEP inhibitor, thiorphan. P-aminohippuric acid (PAH) and inulin were injected into male Sprague-Dawley rats. Vehicle (n = 8) or thiorphan (30 mg/kg, n = 10) was injected after the control period. Mean blood pressure (MBP), plasma and urinary PAH, inulin, NOx and cGMP, urinary volume (UV) and urinary sodium excretion (UNaV) were measured before and after injection of the reagents. MBP, renal plasma flow and glomerular filtration rate were not affected by thiorphan. Plasma NOx and cGMP with thiorphan did not differ from the vehicle, while urinary NOx and cGMP increased. None of the variables were affected by vehicle. UV and UNaV were higher with thiorphan than with vehicle. Positive correlation was found between urinary deltaNOx and deltacGMP. Each urinary deltaNOx and deltacGMP was significantly correlated to both deltaUV and deltaUNaV. Urinary NOx and cGMP were increased while maintaining correlations to UV and UNaV, but plasma NOx and cGMP were not affected by thiorphan. This implies that the mechanism of water-sodium excretion induced by NEP inhibitor is mediated by renal NO. Therefore, renal NO may contribute to the diuretic and natriuretic effects of renal kinins.
Takagawa
Y
Y
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Ura
N
N
Nanba
M
M
Agata
J
J
Higashiura
K
K
Torii
T
T
Takada
M
M
Shimamoto
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000502:physiology; D004231:Diuresis / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000378:metabolism*; D007705:Kinins / Q000494:pharmacology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D015260:Neprilysin / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000097:blood / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D015290:Second Messenger Systems / Q000502:physiology; D015244:Thiorphan / Q000494:pharmacology; D014563:Urodynamics / Q000187:drug effects
D004791:Enzyme Inhibitors; D007705:Kinins; D009569:Nitric Oxide; D015244:Thiorphan; D015260:Neprilysin; D006152:Cyclic GMP