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

Summary We have shown previously that long‐term oestrogen ( E 2) 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 E 2 effects. We evaluated changes in BP , myocardial contractility index ( dP /dt max ) and power spectral indices of haemodynamic variability following selective inhibition of endothelial (e) NOS with N 5 ‐(1‐iminoethyl)‐ l ‐ornithine ( l ‐ NIO ), neuronal (n) NOS with N ω ‐propyl‐ l ‐arginine ( NPLA ) or i NOS with 1400W in telemetered OVX rats treated for 16 weeks with ( OVXE 2) or without (control; OVXC ) E2. The OVXE 2 rats exhibited: (i) reduced BP and increased dP /dt max ; (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 ( IBI LF/HF ); and (iii) reduced LF oscillations of systolic BP , suggesting a reduced vasomotor sympathetic tone. Inhibition of e NOS ( l ‐ NIO ; 20 mg/kg, i.p.) elicited a shorter‐lived pressor response in OVXE 2 than OVXC , rats along with reductions in d P /dt max 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 IBI LF/HF ratio in OVXE 2 but not OVXC rats. The i NOS inhibitor 1400W (5 mg/kg, i.p.) caused no haemodynamic changes in OVXC or OVXE 2 rats. Overall, constitutive NOS isoforms exert restraining tonic modulatory BP effects that encompass e NOS ‐mediated reductions and n NOS ‐mediated elevations in BP in OVXE 2 rats. Baroreflex facilitation and dP /dt max reductions may account for the shorter pressor action of l ‐ NIO in E 2‐treated, compared with untreated, OVX rats.