Contribution of vasopressin to progression of chronic renal failure: study in Brattleboro rats.
We have previously shown that a chronic reduction in plasma vasopressin level slowed the progression of chronic renal failure (CRF) in Sprague Dawley rats. The aim of the present study was to determine the respective contribution of pressor (V1) and antidiuretic (V2) effects of vasopressin on progression. Male homozygous Brattleboro rats with hereditary central diabetes insipidus were submitted to 5/6 nephrectomy. They were divided into three groups, two of which received chronic i.p. infusion of AVP (V1 + V2 effects) or dDAVP (V2 effects). The third group served as control (CONT). The doses of AVP and dDAVP were chosen so as to produce urine osmolality similar to that observed in 5/6 Nx Sprague Dawley rats. All rats ate the same amount of food and drank water ad libitum. Renal function was studied for 13 weeks. All three groups showed a marked hypertension. Rats infused with dDAVP, but not those infused with AVP, had a higher creatininemia, anemia and urinary protein excretion than CONT rats. In the dDAVP but not the AVP group, fractional excretion of urea was markedly decreased and plasma urea concentration rose much more than that of creatinine. These results show that V2 but not V1 effects play a major role in the deleterious influence of vasopressin on progression, at least in Brattleboro rats. The more severe progression seen in dDAVP rats could indirectly result from the V2-mediated effects on the collecting duct resulting in a decreased efficiency of urea excretion, an increased intrarenal urea recycling, and a rise in plasma urea concentration. Both the toxic effects of urea and the recently demonstrated V2-mediated increase in glomerular hemodynamics might be involved in the deleterious influence of V2 agonism.
Bouby
N
N
INSERM Unité 367, Paris, France.
Hassler
C
C
Bankir
L
L
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003919:Diabetes Insipidus / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D011507:Proteinuria / Q000503:physiopathology; D051381:Rats; D011910:Rats, Brattleboro; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000503:physiopathology; D014667:Vasopressins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D014667:Vasopressins; D001127:Arginine Vasopressin; C025044:argipressin, beta-mercapto-beta,beta cyclopentamethylenepropionic acid(1)-; D003404:Creatinine