Chronic administration of adrenomedullin attenuates the hypertension and increases renal nitric oxide synthase in Dahl salt-sensitive rats.
Adrenomedullin reduces systemic blood pressure and increases urinary sodium excretion partly through the release of nitric oxide. We hypothesized that chronic adrenomedullin infusion ameliorates salt-sensitive hypertension and increases the expression of renal nitric oxide synthase (NOS) in Dahl salt-sensitive (DS) rats, because the reduced renal NOS expression promotes salt sensitivity. DS rats and Dahl salt-resistant (DR) rats were fed a high sodium diet (8.0% NaCl) for 3 weeks. The high sodium diet resulted in an increase in blood pressure and a reduction of urinary sodium excretion in association with increased renal adrenomedullin concentrations and decreased expression of renal neuronal NOS (nNOS) and renal medullary endothelial NOS (eNOS) in DS rats compared with DR rats. Chronic adrenomedullin infusion partly inhibited the increase of blood pressure and proteinuria in association with a restoration of renal nNOS and medullary eNOS expression in DS rats under the high sodium diet. The immunohistochemical analysis revealed that the restored renal nNOS expression induced by chronic adrenomedullin infusion may reflect the restoration of nNOS expression in the macula densa and inner medullary collecting duct. These results suggest that adrenomedullin infusion has beneficial effects on this hypertension probably in part through restored renal NOS expression in DS rats.
Yoshihara
Fumiki
F
Division of Hypertension and Nephrology, National Cardiovascular center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. fyoshi@ri.ncvc.go.jp
Suga
Shin-ichi
S
Yasui
Naomi
N
Horio
Takeshi
T
Tokudome
Takeshi
T
Nishikimi
Toshio
T
Kawano
Yuhei
Y
Kangawa
Kenji
K
D053607:Adrenomedullin; D000818:Animals; D015153:Blotting, Western; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats
D010455:Peptides; D053607:Adrenomedullin; D019001:Nitric Oxide Synthase