Mechanisms of renal effects of different agents stimulating production of cGMP.
The effect of agents stimulating the production of guanosine 3',5'-cyclic monophosphate (cGMP) by different mechanisms was compared in conscious unrestrained Wistar rats by administration of infusions of acetylcholine (ACh), sodium nitroprusside (SNP), and atrial natriuretic peptide (ANP). ACh (10 micrograms.kg-1.min-1, n = 8), SNP (200 micrograms.kg-1.min-1, n = 8), and ANP (0.5 micrograms.kg-1.min-1, n = 7) induced natriuresis (urinary Na gradient: 399, 499, and 504 microeq/h, respectively; P less than 0.001 with respect to baseline) and diuresis (urine volume gradient: 0.87, 0.82, and 0.92 ml/h, respectively; P less than 0.001). Urinary cGMP increased (P less than 0.001) with the three agents (delta pmol cGMP/min: ACh 22.3, SNP 42.5, and ANP 48.4); in addition, a parallel increase in renal cGMP content was observed with the three agents (ACh 1.6, SNP 2.8, and ANP 3.5 times with respect to controls; P less than 0.05). Mean arterial pressure did not change with the aforementioned dose of ANP but decreased by 10 and 40% with ACh and SNP, respectively. Glomerular filtration rate increased by a similar magnitude with the three compounds. The competitive inhibitor of L-arginine, N omega-nitro-L-arginine (L-NNA), significantly decreased the diuretic, natriuretic, and hypotensive effects of ACh without affecting the actions of SNP and ANP.(ABSTRACT TRUNCATED AT 250 WORDS)
Grandes
S
S
Laboratorio de Nefrología, Fundación Jiménez Díaz, Madrid, Spain.
Gallego
M J
MJ
Riesco
A
A
López Farré
A
A
Millas
I
I
Casado
S
S
Hernando
L
L
Caramelo
C
C
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis*; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects
D009599:Nitroprusside; D019335:Nitroarginine; D009320:Atrial Natriuretic Factor; D001120:Arginine; D006152:Cyclic GMP; D000109:Acetylcholine