Effects of hyperosmolality on ANP-stimulated cGMP generation in rat inner medullary collecting duct.
The inner medullary collecting duct (IMCD) is a major target site of atrial natriuretic peptide (ANP) for diuresis and natriuresis, and it is in a hypertonic condition made by the renal countercurrent multiplication system. We investigated the effects of hyperosmolality on ANP-stimulated cGMP generation in IMCD and glomerulus. Hypertonic solutions (490 and 690 mOsm/kg.H2O) were made by adding NaCl or urea to isotonic solution (290 mOsm/kg.H2O). Hypertonicity of 490 mOsm/kg.H2O using NaCl reduced both ANP-stimulated guanylate cyclase activity (from 7.7 +/- 1.1 to 4.1 +/- 0.5 fmol/mm/5 min) and cGMP generation (from 1.35 +/- 0.18 to 0.48 +/- 0.20 fmol/mm/3 min) in IMCD. Hypertonicity of 690 mOsm/kg.H2O using NaCl did not further reduce ANP-stimulated cGMP generation in IMCD. Hypertonicity using urea also inhibited ANP-stimulated guanylate cyclase activity and cGMP generation in IMCD. On the other hand, hypertonicity using NaCl stimulated AVP-stimulated cAMP generation in IMCD, while hypertonicity using urea reduced it. In glomeruli, hyperosmolality of 490 mOsm/kg.H2O using NaCl also reduced ANP-stimulated cGMP generation, and hypertonicity of 690 mOsm/kg.H2O using NaCl further reduced it. In summary, hyperosmolality using NaCl and urea inhibited ANP-sensitive guanylate cyclase activity and cGMP generation both in IMCD and glomeruli. However, the mechanisms at work may be different between NaCl and urea.
Shinohara
M
M
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Nonoguchi
H
H
Ujiie
K
K
Terada
Y
Y
Owada
A
A
Tomita
K
K
Marumo
F
F
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects* / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D014508:Urea / Q000494:pharmacology
D012462:Saline Solution, Hypertonic; D001127:Arginine Vasopressin; D009320:Atrial Natriuretic Factor; D014508:Urea; D006162:Guanylate Cyclase; D006152:Cyclic GMP