Renoprotective effects of omapatrilat are mediated partially by bradykinin.
OBJECTIVE
To investigate the effects of omapatrilat on systemic and renal hemodynamics, glomerular dynamics, renal function, and histopathological changes as well as the participation of the bradykinin B2 receptor in WKY, SHR, and L-NAME/SHR rats.


METHODS
Eight groups of 17-week-old rats were examined using renal micropuncture techniques and histopathological analyses after 3 weeks of treatment: group 1, WKY control; group 2, WKY+omapatrilat (40 mg/kg/day); group 3, SHR control; group 4, SHR+omapatrilat; group 5, SHR+L-NAME (50 mg/l); group 6, SHR+L-NAME+omapatrilat; group 7, SHR+L-NAME for 3 weeks followed by omapatrilat for a subsequent 3 weeks, and group 8, SHR+L-NAME+omapatrilat+bradykinin antagonist icatibant (500 microg/kg/day).


RESULTS
In WKY and SHR, omapatrilat significantly reduced the mean arterial pressure, increased effective renal blood flow and single nephron plasma flow associated with reduced glomerular arteriolar resistances. Furthermore, omapatrilat prevented and reversed L-NAME induced urinary protein excretion, glomerular and arteriolar injuries, glomerular morphometric alterations, and glomerular apoptosis (at least, p < 0.05). Icatibant partially inhibited these beneficial effects of omapatrilat.


CONCLUSIONS
Omapatrilat provided potent antihypertensive and renoprotective actions, which were mediated, in part, by bradykinin.
Zhou
Xiaoyan
X
Hypertension Research Laboratories, Ochsner Clinic Foundation, New Orleans, LA 70121, USA.
Ono
Hidehiko
H
Ono
Yuko
Y
Frohlich
Edward D
ED
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009399:Nephrons / Q000098:blood supply; D015260:Neprilysin / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017597:Renal Blood Flow, Effective / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D013841:Thiazepines / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; D011480:Protease Inhibitors; D011725:Pyridines; D013841:Thiazepines; C106266:omapatrilat; C065679:icatibant; D008666:Metalloendopeptidases; D015260:Neprilysin; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester