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

Abstract

Summary We have previously shown that long-term estrogen (E2) replacement lowers blood pressure (BP) and improves the cardiovascular autonomic control in ovariectomized (OVX) rats. In this study, we investigated whether constitutive and/or inducible nitric oxide synthase (NOS) modulate these E2 effects.We evaluated changes in BP, myocardial contractility index (dP/dtmax), and power spectral indices of hemodynamic variability following selective inhibition of eNOS [N5-(1-iminoethyl)-L-ornithine; L-NIO], nNOS (Nω-propyl-L-arginine; NPLA), or iNOS (1400W) in telemetered OVX rats treated for 16 weeks with (OVXE2) or without (control, OVXC) E2.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.eNOS inhibition (L-NIO, 20 mg/kg i.p.) elicited a shorter-lived pressor response in OVXE2, than in OVXC, rats along with reductions in dP/dtmax and increases in the spectral index of spontaneous baroreflex sensitivity (index α). NPLA (1 mg/kg i.p.) reduced BP and increased IBILF/HF ratio in OVXE2, but not OVXC rats. The iNOS inhibitor 1400W (5 mg/kg i.p.) caused no hemodynamic changes in OVXC or OVXE2 rats.Overall, constitutive NOS isoforms exert restraining tonic modulatory BP effects, which encompass eNOS-mediated reduction and nNOS-mediated elevation in BP in OVXE2 rats. Baroreflex facilitation, and dP/dtmax reductions might account for the shorter pressor action of L-NIO in E2-treated, compared with untreated, OVX rats.

Chronic Ethanol Vapor Exposure Potentiates the Cardiovascular Responses to Acute Stress in Male but Not in Female Rats

“…In fact, as stated above, we demonstrated increased cardiac parasympathetic activity in female but not in male rats exposed to chronic ethanol vapor inhalation [21]. Further, other studies observed that this effect on cardiac vagal tone was estrogen-dependent [36,84,85]. For example, El-mas and Abdel-rahman [36] showed that the parasympathetic overactivity induced by chronic ethanol was exacerbated in estrogen-replaced ovariectomized rats, when compared to ovariectomized ones.…”

Chronic ethanol vapor exposure potentiates cardiovascular responses to acute stress in male but not in female rats

“…In fact, as stated above, we demonstrated increased cardiac parasympathetic activity in female but not in male rats exposed to chronic ethanol vapor inhalation [21]. Furthermore, other studies observed that this effect on cardiac vagal tone was estrogen-dependent [36,104,105]. For example, El-mas and Abdelrahman [36] showed that the parasympathetic overactivity induced by chronic ethanol was exacerbated in estrogen-replaced ovariectomized rats, when compared to ovariectomized ones.…”

Prolonged Exposure to Alcohol Vapor Causes Change in Cardiovascular Function in Female but not in Male Rats

“…Despite the increased HR, we did not identify changes in MAP of female controls. It has been extensively explained in studies that an estrogen protective effect upon MAP occurs due to its actions in the kidney (e.g., females have higher levels of the vasodilator angiotensin compared to males) (Bhatia et al., ; Brosnihan et al., ; Brown et al., ; Shenoy et al., ; Xue et al., ) and on nitric oxide (NO) production in the heart and vasculature (Abdel‐rahman, ; Caulin‐Glaser et al., ; Chen et al., ; El‐Mas and Abdel‐Rahman, ; Mendelsohn and Karas, ; Wang and Abdel‐Rahman, ). It has also been proposed that although female rats show an increase in HR, the MAP would not be altered because of the sex differences in control of baroreflex responses by the nucleus of the solitary tract (NTS), nucleus ambiguous (NA), parabrachial nucleus (PBN), and caudal and rostral ventrolateral medulla (Abdel‐rahman, ; Mohamed et al., ; Wyss and Carlson, ; Xue et al., ).…”

“…Different methods to expose rats to alcohol have been used to study the consequences of chronic EtOH exposure on cardiovascular function (Crestani et al., ; El‐Mas and Abdel‐Rahman, ; Engi et al., ; Russ et al., ). However, many studies have demonstrated that alcohol vapor exposure provides a particular advantage over other methods (Gilpin et al., , ; Meinhardt and Sommer, ; Vendruscolo and Roberts, ).…”