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Background: A greater frequency of vasomotor symptoms (VMSs) has been associated with higher low-density lipoprotein cholesterol (LDL-C), but the association with high-density lipoprotein cholesterol (HDL-C) remains unclear. Endogenous estradiol (E2) levels are associated with both VMS and lipid levels and thus may confound such associations., Objectives: To assess the relationship of VMS frequency with HDL-C, LDL-C, and lipoprotein concentrations (HDL and LDL particles [HDL-P; LDL-P]) and lipoprotein sizes in midlife women and to evaluate whether these associations are explained by E2., Methods: Participants were from the Study of Women's Health Across the Nation (SWAN) HDL ancillary study who had both nuclear magnetic resonance (NMR) spectroscopy lipoprotein subclass metrics and self-reported frequency of VMS measured 2-5 times over the menopause transition. VMS frequency was categorized into none, 1-5 days (infrequent), or ≥6 days (frequent) within the past 2 weeks., Results: We evaluated 522 women [at baseline: mean age 50.3 (SD: 2.8) years; infrequent VMS: 29.8%, frequent VMS: 16.5%]. Adjusting for potential confounders except E2, frequent VMS was associated with smaller HDL size [β(SE): -0.06 (0.03); P = .04] and higher concentrations of LDL-C [β(SE): 3.58 (1.77); P = .04] and intermediate LDL-P [β(SE): 0.09 (0.05); P = .04] than no VMS. These associations were largely explained by E2, all P's > .05., Conclusions: Frequent VMSs were associated with smaller HDL size and higher concentrations of LDL-C and intermediate LDL-P. These associations were explained by endogenous E2. Whether treating frequent VMS with exogenous E2 could simultaneously improve lipids/lipoproteins profile should be assessed in future studies., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Cardiovascular dysfunction usually occurs after high thoracic and cervical spinal cord injury (SCI). The disruption of supraspinal vasomotor pathways (SVPs) results in the loss of bulbospinal regulation of sympathetic preganglionic neurons, leading to hypotension and compensatory tachycardia at rest. Episodic autonomic dysreflexia can develop upon sensory stimulation below the level of injury. In rodents, the precise spatial distribution of SVPs in the spinal cord originating from the rostral ventrolateral medulla (RVLM) has not been fully defined. To facilitate future studies of axon regeneration to regain cardiovascular control, we injected biotinylated dextran amine (BDA) bilaterally into the RVLM to anterogradely trace SVPs in Fischer 344 (F344) rats. Three weeks later, BDA-labeled descending projections were predominantly localized within the dorsolateral funiculus throughout the cervical and thoracic spinal segments as expected. Additionally, BDA-labeled fibers were also observed in ventral white matter. After a T4 dorsal hemisection to interrupt the dorsolateral funiculus, BDA labeled terminals originating from the ventral white matter as well as serotonergic projections were still detected in regions of autonomic nuclei below the injury. Based on these results, we examined cardiovascular responses after different lesions at spinal level T4, including lateral or dorsal hemisection, dorsolateral or complete transection. Hemodynamic dysfunction and autonomic dysreflexia were only elicited in rats with complete T4 transections when all SVPs were disrupted. Hence, F344 rats with complete T4 transections provide a reliable model for investigating means to improve cardiovascular functional recovery after SCI., (Published by Elsevier B.V.)

The effects of an intracoronary infusion of N(G)-monomethyl-L-arginine (LNMMA) followed by intracoronary administration of nitroglycerin in non-stenotic proximal and distal coronary segments were studied in 11 patients with coronary artery disease and in 19 subjects with "normal arteriograms". In normal subjects, LNMMA induced significant constriction (p<0.01) of proximal and distal vessels in non-smokers and smokers. In normal non-smokers, the reduction in coronary luminal diameter of proximal segments was significantly greater compared to normal smokers (p<0.05). In patients with coronary artery disease, LNMMA induced significant constriction of proximal and distal vessels in smokers, and only distal constriction in non-smokers (p<0.01). The reduction in coronary luminal diameter of the distal segments in normal smokers, and in both groups in patients with coronary artery disease was significantly greater compared with proximal segments (p<0.05). Therefore, the difference in vasomotor response to LNMMA in relation to smoking is localised to the proximal coronary segments.

Background: A model of shunt-induced pulmonary hypertension was used to study the effects of pulmonary overcirculation on endothelial nitric oxide synthase (eNOS) and cytochrome P450-4A (cP450-4A) vasodilatory mechanisms and related hemodynamic responses., Methods: An aortopulmonary shunt was constructed in 6-week-old piglets (n = 7, sham-operated controls n = 8). Hemodynamic measurements were made 4 weeks later under serial experimental conditions: baseline (fractional concentration of oxygen, 0.4); inhaled nitric oxide, 25 ppm (INO); hypoxia (fractional concentration of oxygen, 0.14); hypoxia + INO; N(omega)-nitro-L-arginine methylester (L-NAME 30 mg/kg intravenously, competitive NOS inhibitor); and L-NAME + INO. Lung protein levels of eNOS and cP450-4A and NOS activity were compared between groups., Results: Shunted animals had a higher baseline pulmonary artery pressure (p < 0.05). L-NAME resulted in a greater increase in pulmonary vascular resistance in shunted animals (150% +/- 26% shunt versus 69% +/- 14% control; p = 0.01). The INO administered during baseline conditions decreased pulmonary vascular resistance only in control animals (p < 0.05). Protein levels of eNOS and NOS activity were similar in both groups; however, cP450-4A protein levels were decreased in the shunted group (p = 0.02)., Conclusions: The NO production was preserved in shunted animals but they demonstrated greater vasodilatory dependence on NO, evidenced by an exaggerated increase in pulmonary vascular resistance after NOS inhibition. Loss of the cP450-4A vasodilatory system may be the driving force for NO dependency in the shunted pulmonary circulation.