Effects of omapatrilat on blood pressure and renal injury in L-NAME and L-NAME plus DOCA-treated rats.
BACKGROUND
This study investigates the effects of chronic administration of omapatrilat (OMA) on blood pressure (BP), renal injury, and other variables in N(omega)-nitro-L-arginine methyl ester (L-NAME) hypertension and in the low-renin model produced by the simultaneous administration of L-NAME and deoxycorticosterone acetate (DOCA).


METHODS
The control, DOCA, L-NAME, L-NAME + DOCA, L-NAME + OMA, and L-NAME + DOCA + OMA groups were used. Tail systolic BP was measured twice a week. After 4 weeks of treatment, mean arterial pressure (MAP), and metabolic, morphologic, and renal variables were measured.


RESULTS
The final values of MAP were 109 +/- 5.1 mm Hg for the control group, 113 +/- 3.0 mm Hg for DOCA, 175 +/- 3.7 mm Hg for L-NAME, 193 +/- 3.8 mm Hg for L-NAME + DOCA, 117 +/- 3.9 mm Hg for L-NAME + OMA, and 158 +/- 3.0 mm Hg for L-NAME + DOCA + OMA. The rats treated with L-NAME showed mild and scarce renal lesions, which were prevented by OMA treatment and the L-NAME + DOCA group showed proteinuria and hyaline arteriopathy, which were markedly attenuated in the L-NAME + DOCA + OMA group. Plasma urea and creatinine were significantly increased in the L-NAME + DOCA group, whereas these variables were not significantly greater in the L-NAME + DOCA + OMA group versus controls. The L-NAME + DOCA group showed relative renal and cardiac hypertrophy that was not observed in the L-NAME + DOCA + OMA group.


CONCLUSIONS
The simultaneous blockade of neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE) completely prevents L-NAME hypertension. Our results also show that OMA attenuates the increased BP and the renal injury in L-NAME hypertensive rats treated with DOCA. Assuming that this is a low-renin model of hypertension, the protective effect of OMA may be due to an increase in vasodilator peptides produced by both ACE and NEP inhibition.
Rodriguez-Gomez
Isabel
I
Departamento de Fisiología, Unidad Experimental, Servicio de Nefrología, Hospital Virgen de las Nieves, Granada, Spain.
Wangensteen
Rosemary
R
Atucha
Noemi M
NM
O'Valle
Francisco
F
Del Moral
Raimundo G
RG
Garcia-Estañ
Joaquin
J
Vargas
Felix
F
Osuna
Antonio
A
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors; D006977:Hypertension, Renal / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000097:blood; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood; D013841:Thiazepines / Q000494:pharmacology*; D014508:Urea / Q000097:blood
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D011725:Pyridines; D013841:Thiazepines; C106266:omapatrilat; D003900:Desoxycorticosterone; D014508:Urea; D012964:Sodium; D003404:Creatinine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester