title: Intracerebroventricular infusion of hypertonic NaCl increases urinary CGMP in healthy and cirrhotic rats.
abstract: Implication of serum atrial natriuretic peptide (ANP) and endothelin-1 (ET1) in the central nervous system (CNS)-induced natriuresis and hypertension respectively, was investigated in healthy and cirrhotic rats. Both healthy and nonascitic CCl(4)-induced cirrhotic rats under pentobarbital anesthesia received either normotonic (140 mmol/L) or hypertonic (320 mmol/L) NaCl artificial cerebrospinal fluid into the CNS lateral ventricle at a rate of 8.3 microl/min for 120 min. A sham operated group, but not centrally infused, served as matched control. Hypertonic NaCl solution significantly increased mean arterial pressure (MAP) similarly in both healthy (n = 5) ((MAP: 16 mm Hg, 13%) and cirrhotic rats (n = 6) ((MAP: 20 mm Hg, 15%) (ANOVA, p <.001) although the latter showed a slower increment. Under hypertonic NaCl infusion, natriuresis was also significantly increased in a similar manner in both healthy (U (Na) V: baseline: 0.38 +/- 0.22 micromol/min x 100 g; experiment: 2.36 +/- 0.90 micromol/min x 100 g; mean +/- SD) and cirrhotic rats (0.69 +/- 0.48 vs. 3.16 +/- 0.87; p <.001). By contrast, central hypertonic NaCl solutions did not show a significant modification of serum ANP in neither healthy (62 +/- 18 fmol/ml vs. 51 +/- 17 fmol/ml) nor cirrhotic rats (126 +/- 61 vs. 115 +/- 30). Likewise, ET-1 was not significantly modified under central hypertonic NaCl infusion in neither healthy (352 +/- 46 pg/ml vs. 344 +/- 39 pg/ml) nor cirrhotic rats (287 +/- 58 vs. 277 +/- 61). Despite no modification in serum ANP, there was a significant increment in urinary excretion of cGMP under central hypertonic NaCl infusions in bo th healthy (6.8 +/- 4.1 pmol/min x 100 g vs. 13.0 +/- 6.5 pmol/min x 100 g; p <.05) and cirrhotic rats (8.6 +/- 1.7 vs. 11.1 +/- 1.3; p <.05). Our data indicate the preservation of the mechanisms of central natriuresis in a model of non-ascitic CCl(4 )-induced cirrhosis in rats. An increment in urinary cGMP could potentially be implicated in the natriuretic response obtained by intracerebroventricular hypertonic NaCl stimulus in both healthy and cirrhotic rats. The lack of modification of serum ANP and ET-1 does not appear to support a systemic implication of these peptides in the natriuretic and hypertensive responses respectively induced by this manoeuvre.
authors.affiliation: Division of Nephrology and Internal Medicine, Clínica Universitaria, University of Navarra, Pamplona, Spain. lbolanosc@senefro.org
authors.forename: L
authors.initials: L
authors.lastname: Bolaños
authors.forename: I
authors.initials: I
authors.lastname: Colina
authors.forename: A
authors.initials: A
authors.lastname: Purroy
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002251:Carbon Tetrachloride; D006152:Cyclic GMP / Q000378:metabolism* / Q000652:urine; D019332:Endothelin-1 / Q000097:blood; D005355:Fibrosis / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000378:metabolism*; D012964:Sodium / Q000652:urine; D012965:Sodium Chloride / Q000008:administration & dosage / Q000378:metabolism*; D013997:Time Factors
chemical_list: D019332:Endothelin-1; D012462:Saline Solution, Hypertonic; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D012964:Sodium; D002251:Carbon Tetrachloride; D006152:Cyclic GMP