Influence of irbesartan and enalapril on changes of renal function associated with the established phase of l-NAME hypertension.
OBJECTIVE
Reversibility of the systemic and renal alterations induced by N(omega)-nitro-L-arginine-methyl ester(L-NAME) was assessed by treatment with irbesartan and enalapril (30 and 10 mg/kg per 24 h, respectively) alone or in combination.


METHODS
L-NAME (20 mg/kg per 24 h) was given to rats for 6 weeks and treatments were administered during the last 2 weeks. Glomerular filtration rate and renal plasma flow [GFR and RPF per g of kidney weight (KW)] were determined using the clearance technique.


RESULTS
Arterial pressure was similarly reduced by treatments. GFR was lower in L-NAME-treated rats than in controls (552 +/- 52 versus 1106 +/- 78 microl/min per g KW), whereas RPF was reduced to a larger extent, thus resulting in an increase in filtration fraction. GFR was normalized by irbesartan but not enalapril or the combination (1042 +/- 50, 790 +/- 79 and 725 +/- 38 microl/min per g KW, respectively). RPF returned to normal and filtration fraction fell markedly with the combination. All treatments reduced the lesions of preglomerular vessels and reversed L-NAME-induced albuminuria and cardiovascular hypertrophy. At a dose of 3 mg/kg per 24 h, irbesartan only reduced the lesions of the afferent arteriole.


CONCLUSIONS
Through its effects on AT1 receptors, angiotensin II may play an important role in the maintenance of L-NAME hypertension and associated alterations. The lower GFR and filtration fraction observed with enalapril in the presence of irbesartan suggests the intervention of non-angiotensin II-mediated mechanism, and at the postglomerular level, in the effect of angiotensin-converting enzyme (ACE) inhibitors.
Jover
B
B
Groupe Rein et Hypertension, Université de Montpellier I, Montpellier, France. jover@iurc1.iurc.montp.inserm.fr
Herizi
A
A
Casellas
D
D
Mimran
A
A
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure; D001808:Blood Vessels / Q000473:pathology; D002319:Cardiovascular System / Q000473:pathology; D004338:Drug Combinations; D004656:Enalapril / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D006439:Hemodynamics; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D012079:Renal Circulation; D013623:Tail / Q000098:blood supply; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D004656:Enalapril; D000077405:Irbesartan; D019331:NG-Nitroarginine Methyl Ester