Endothelial and neuronal nitric oxide synthases variably modulate the oestrogen-mediated control of blood pressure and cardiovascular autonomic control

Abstract

We have shown previously that long-term oestrogen (E2) replacement lowers blood pressure (BP) and improves cardiovascular autonomic control in ovariectomized (OVX) rats. In the present study, we investigated whether constitutive and/or inducible (i) nitric oxide synthase (NOS) modulate these E2 effects. We evaluated changes in BP, myocardial contractility index (dP/dtmax) and power spectral indices of haemodynamic variability following selective inhibition of endothelial (e) NOS with N5-(1-iminoethyl)- l-ornithine (l-NIO), neuronal (n) NOS with Nω-propyl-l-arginine (NPLA) or iNOS with 1400W in telemetered OVX rats treated for 16 weeks with (OVXE2) or without (control; OVXC) E2. The OVXE2 rats exhibited: (i) reduced BP and increased dP/dtmax; (ii) cardiac parasympathetic dominance, as reflected by the reduced low-frequency (LF; 0.25-0.75 Hz)/high-frequency (HF; 0.75-3 Hz) ratio of interbeat intervals (IBILF/HF); and (iii) reduced LF oscillations of systolic BP, suggesting a reduced vasomotor sympathetic tone. Inhibition of eNOS (l-NIO; 20 mg/kg, i.p.) elicited a shorter-lived pressor response in OVXE2 than OVXC, rats along with reductions in dP/dtmax and increases in the spectral index of spontaneous baroreflex sensitivity (index α). Treatment with 1 mg/kg, i.p., NPLA reduced BP and increased the IBILF/HF ratio in OVXE2 but not OVXC rats. The iNOS inhibitor 1400W (5 mg/kg, i.p.) caused no haemodynamic changes in OVXC or OVXE2 rats. Overall, constitutive NOS isoforms exert restraining tonic modulatory BP effects that encompass eNOS-mediated reductions and nNOS-mediated elevations in BP in OVXE2 rats. Baroreflex facilitation and dP/dtmax reductions may account for the shorter pressor action of l-NIO in E2-treated, compared with untreated, OVX rats. © 2014 Wiley Publishing Asia Pty Ltd.