Acute hypotensive effect of diminazene aceturate in spontaneously hypertensive rats: role of NO and Mas receptor.

Abstract

Diminazene aceturate (DIZE) has been described as an angiotensin-converting enzyme 2 (ACE2) activator. We aimed to investigate DIZE effects on blood pressure (BP) of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. BP was recorded in awake and unrestrained rats 24hours after femoral artery catheterization. DIZE (15mg/kg, s.c.) produced a fast BP decrease only in SHR (P<.01). Pre-treatment with L-NAME (10mg/kg, iv) did not change the hypotensive effect on systolic BP whereas mitigated the DIZE effect on diastolic BP (∆ Emax: -31±5 DIZE vs -15±1mmHg DIZE+L-NAME, P<.05). BP changes after DIZE remained unchanged after the treatment of rats with A-779 (50ug/kg, iv), a Mas receptor blocker. Vasodilatation curves to DIZE (10-9 to 10-4 mol/L) in mesenteric arteries confirmed the NO-mediation on DIZE effects in SHR, as L-NAME (300μmol/L) reduced the vascular sensitivity (∆EC50: -5.12±0.09 CONTROL vs -4.66±0.08 L-NAME, P<.05) and the magnitude of DIZE effect (area under the curve (AUC), 357.5±8.2 DIZE vs 424.7±11.6 L-NAME; P<.001), whereas A-779 (1μmol/L) enhanced DIZE response (AUC, 357.5±8.2 DIZE vs 309.8±14.7 A-779, P<.05). Our findings indicate that DIZE acutely reduces the BP in SHR possibly by a mechanism other than Mas receptor activation. This effect seems to be mediated, at least partially, by NO.