Vascular Dysfunction
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2021 ◽  
pp. 1-11
Soyoung Cheon ◽  
Jeremy C. Tomcho ◽  
Jonnelle M. Edwards ◽  
Nicole R. Bearss ◽  
Emily Waigi ◽  

Recent studies have shown that chronic use of prescription or illicit opioids leads to an increased risk of cardiovascular events and pulmonary arterial hypertension. Indices of vascular age and arterial stiffness are also shown to be increased in opioid-dependent patients, with the effects being more marked in women. There are currently no studies investigating sex-specific vascular dysfunction in opioid use, and the mechanisms leading to opioid-induced vascular damage remain unknown. We hypothesized that exposure to exogenous opioids causes sex-specific vascular remodeling that will be more pronounced in female. Acknowledging the emerging roles of cofilins and extracellular signal-regulated kinases (ERKs) in mediating actin dynamics, we investigated the effects of morphine on these molecules. Twenty-four hour exposure to morphine increased inactivated cofilin and activated ERKs in resistance arteries from female mice, which may promote stress fiber over-assembly. We also performed continuous intraluminal infusion of morphine in pressurized resistance arteries from male and female mice using culture pressure myographs. We observed that morphine reduced the vascular diameter in resistance arteries from female, but not male mice. These results have significant implications for the previously unexplored role of exogenous opioids as a modifiable cardiovascular risk factor, especially in women.

Life Sciences ◽  
2021 ◽  
pp. 119965
Nisita Chaihongsa ◽  
Putcharawipa Maneesai ◽  
Weerapon Sangartit ◽  
Prapassorn Potue ◽  
Sarawoot Bunbupha ◽  

2021 ◽  
Vol 25 ◽  
pp. e50
Bianca R. Fato ◽  
Natasha De Alwis ◽  
Natalie K. Binder ◽  
Sally Beard ◽  
Stephen Tong ◽  

2021 ◽  
pp. 101019
Paola Valero ◽  
Gonzalo Fuentes ◽  
Marcelo Cornejo ◽  
Sofía Vega ◽  
Adriana Grismaldo ◽  

2021 ◽  
Vol 2 ◽  
Andrew V. Kuczmarski ◽  
Laura M. Welti ◽  
Kerrie L. Moreau ◽  
Megan M. Wenner

Aging is a primary risk factor for cardiovascular disease (CVD), which is the leading cause of death in developed countries. Globally, the population of adults over the age of 60 is expected to double by the year 2050. CVD prevalence and mortality rates differ between men and women as they age in part due to sex-specific mechanisms impacting the biological processes of aging. Measures of vascular function offer key insights into cardiovascular health. Changes in vascular function precede changes in CVD prevalence rates in men and women and with aging. A key mechanism underlying these changes in vascular function is the endothelin (ET) system. Studies have demonstrated sex and sex hormone effects on endothelin-1 (ET-1), and its receptors ETA and ETB. However, with aging there is a dysregulation of this system resulting in an imbalance between vasodilation and vasoconstriction. Thus, ET-1 may play a role in the sex differences observed with vascular aging. While most research has been conducted in pre-clinical animal models, we describe more recent translational data in humans showing that the ET system is an important regulator of vascular dysfunction with aging and acts through sex-specific ET receptor mechanisms. In this review, we present translational evidence (cell, tissue, animal, and human) that the ET system is a key mechanism regulating sex-specific changes in vascular function with aging, along with therapeutic interventions to reduce ET-mediated vascular dysfunction associated with aging. More knowledge on the factors responsible for the sex differences with vascular aging allow for optimized therapeutic strategies to attenuate CVD risk in the expanding aging population.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Jessica L Faulkner ◽  
Derrian Wright ◽  
Simone Kennard ◽  
Galina Antonova ◽  
Iris Z Jaffe ◽  

Placental ischemia, an initiating event of preeclampsia (PE), increases plasma leptin levels. We recently developed a model of midgestation (gestation day (GD)11-18) leptin infusion mimicking the midgestation rise in leptin levels of PE patients. Our previous work demonstrates that deletion of endothelial mineralocorticoid receptors (ECMR) improves markers of vascular dysfunction in leptin-infused female mice. We hypothesized vascular function improvement with ECMR deletion ablates hypertension and fetal growth restriction in pregnant leptin-infused mice. Pregnant ECMR +/+ (WT) and ECMR -/- (KO) mice were infused with vehicle or leptin by osmotic pump (lep, 0.9mg/kg/day, s.c.) on GD11-18 while implanted with radiotelemeters for conscious blood pressure (BP) measurement and wire myography of thoracic aorta and 2 nd order mesenteric arteries at GD18 (*=P<0.05). Leptin infusion did not decrease maternal weight in any groups. Leptin decreased pup weight (0.86±0.04g WT vs 0.52±0.11 WT+lep*) and placental efficiency (pup/placenta ratio) (9.7±0.7 WT vs 7.9±0.6 WT+lep*) in WT pregnant mice. ECMR deletion prevented leptin-mediated decreases in pup weight (0.91±0.06g KO vs 1.0±0.07 KO+lep) and placental efficiency (9.6±0.5 KO vs 9.4±1.2 KO+lep). Mean arterial pressure (BP) increased in leptin-infused WT (102±3mmHg WT vs 120±12 WT+lep*), but not KO (107±2 KO vs 106±8 KO+lep), mice from GD11-18. Leptin infusion reduced acetylcholine-mediated relaxation in both aorta and mesenteric arteries of WT* and constriction to KCl in mesenteric arteries in WT*, but not KO, pregnant mice (2-way ANOVA, repeated measures). Leptin increased plasma endothelin-1 (ET-1, 1.1±0.3 pg/ml WT vs 4.4±1.8 WT+lep*), placental mRNA expression of prepro-ET-1 (1.9±0.3-fold change from WT*) and ET-1 converting enzyme-1 (1.6±0.3-fold change from WT*) in pregnant WT mice. Leptin infusion also increased adrenal aldosterone-synthase protein (1.4±0.4 WT ratio/β actin vs 3.2±0.3 WT+lep*) and angiotensin II type 1 receptor b (3.5±0.8-fold change from WT*) mRNA in pregnant mice. Collectively, these data indicate that leptin infusion induces hypertension and fetal growth restriction in pregnant mice due to vascular dysfunction and increased ECMR activation in pregnant mice.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Linsay McCallum ◽  
Stefanie Lip ◽  
Francisco J Rios ◽  
Karla B Neves ◽  
Jason Kilmartin ◽  

Hypertension, vascular dysfunction and downregulation of the renin angiotensin system as sequelae of COVID-19 The long-term CV consequences of COVID are unknown however the potential for ongoing cardiac and vascular inflammation with RAAS alteration may increase the risk of developing hypertension and CV disease. Non-hypertensive patients hospitalised in April-May 2020 with either confirmed COVID19 (cases) or non-COVID (controls) diagnosis were recruited ≥12 weeks post-discharge. All underwent detailed BP and vascular/immune and RAAS phenotyping. The primary outcome was ABPM 24-hr SBP. Paired t-tests and multivariable regression models used to assess differences. Thirty cases and eighteen controls completed the study. Cases were older (51±7 vs 45±9 years) with lower discharge SBP (121±10 vs 128±15 mmHg; p0.01). ABPM at study visit was higher in the cases compared to controls (24-hour SBP (OR[95%CI]: 8.6[0.9-16.3]; p0.03), day-time SBP (8.6[1.5-17.3]; p0.02), day-time DBP (4.6[0.1-9.1]; p<0.05). Paired analysis of office BP showed a 11 mmHg difference between cases and controls (11.5[3.12];19.8; p=0.008; figure) Cases had lowerRenin and Ang-1-10 levels (-0.4[-0.9-0.1]; p0.08; -0.7[-1.2- -0.1]; p0.02 respectively) and higher TNF-alpha (0.5[0.1-0.9]; p0.01). Confirmed COVID requiring hospitalisation is associated with elevated SBP, reduced renin and Ang-1-10 and elevated TNF-alpha at ≥12 weeks post-discharge.

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