Vascular dysfunction in the stroke-prone spontaneously hypertensive rat is dependent on constrictor prostanoid activity and Y chromosome lineage

2018 ◽  
Vol 132 (1) ◽  
pp. 131-143 ◽  
Author(s):  
Shanzana I. Khan ◽  
Karen L. Andrews ◽  
Ann-Maree Jefferis ◽  
Garry L. Jennings ◽  
Amanda K. Sampson ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Vascular Function ◽  
Disease Risk ◽  
Spontaneously Hypertensive Rat ◽  
Vascular Dysfunction ◽  
Cardiovascular Disease Risk ◽  
Spontaneously Hypertensive ◽  
Downstream Target ◽  
Hypertensive Rat ◽  
Artery Disease

Vascular dysfunction is a hallmark of hypertension and the strongest risk factor to date for coronary artery disease. As Y chromosome lineage has emerged as one of the strongest genetic predictors of cardiovascular disease risk to date, we investigated if Y chromosome lineage modulated this important facet in the stroke-prone spontaneously hypertensive rat (SHRSP) using consomic strains. Here, we show that vascular dysfunction in the SHRSP is attributable to differential cyclooxygenase (COX) activity with nitric oxide (NO) levels playing a less significant role. Measurement of prostacyclin, the most abundant product of COX in the vasculature, confirmed the augmented COX activity in the SHRSP aorta. This was accompanied by functional impairment of the vasodilatory prostacyclin (IP) receptor, while inhibition of the thromboxane (TP) receptor significantly ameliorated vascular dysfunction in the SHRSP, suggesting this is the downstream target responsible for constrictor prostanoid activity. Importantly, Y chromosome lineage was shown to modulate vascular function in the SHRSP through influencing COX activity, prostacyclin levels and IP dysfunction. Vascular dysfunction in the renal and intrarenal arteries was also found to be prostanoid and Y chromosome dependent. Interestingly, despite no apparent differences in agonist-stimulated NO levels, basal NO levels were compromised in the SHRSP aorta, which was also Y chromosome dependent. Thus, in contrast with the widely held view that COX inhibition is deleterious for the vasculature due to inhibition of the vasodilator prostacyclin, we show that COX inhibition abolishes vascular dysfunction in three distinct vascular beds, with IP dysfunction likely being a key mechanism underlying this effect. We also delineate a novel role for Y chromosome lineage in regulating vascular function through modulation of COX and basal NO levels.

scholarly journals Vascular Alterations Among Young Adults with SARS-CoV-2

2020 ◽  
Author(s):  
Stephen M. Ratchford ◽  
Jonathon Lee Stickford ◽  
Valesha M Province ◽  
Nina Stute ◽  
Marc Andrew Augenreich ◽  
...  
Keyword(s):  
Young Adults ◽  
Arterial Stiffness ◽  
Systemic Inflammation ◽  
Vascular Function ◽  
Disease Risk ◽  
Vascular Dysfunction ◽  
Cardiovascular Disease Risk ◽  
Area Under The Curve ◽  
Control Group ◽  
Cross Sectional

Background: While SARS-CoV-2 primarily affects the lungs, the virus may be inflicting detriments to the cardiovascular system, both directly through angiotensin converting enzyme 2 receptor as well as initiating systemic inflammation. Persistent systemic inflammation may be provoking vascular dysfunction, an early indication of cardiovascular disease risk. Methods: In order to establish the potential effects of SARS-CoV-2 on the systemic vasculature in the arms and legs, we performed a cross-sectional analysis of young healthy adults (Control: 5M/15F, 23.0±1.3y, 167±9cm, 63.0±7.4kg) and young adults who, 3-4 weeks prior to testing, had tested positive for SARS-CoV-2 (SARS-CoV-2: 4M/7F, 20.2±1.1y, 172±12cm, 69.5±12.4kg) (mean±SD). Using Doppler ultrasound, brachial artery flow-mediated dilation (FMD) in the arm and single passive limb movement (sPLM) in the leg were assessed as markers of vascular function. Pulse wave velocity (PWVcf) was assessed as a marker of arterial stiffness. Results: FMD was lower in the SARS-CoV-2 group (2.71±1.21%) compared to the Control group (8.81±2.96%) (P<0.01) and when made relative to the shear stimulus (SARS-CoV-2: 0.04±0.02AU, Control: 0.13±0.06AU, P<0.01). The femoral artery blood flow response, as evidenced by the area under the curve, from the sPLM was lower in the SARS-CoV-2 group (-3±91ml) compared with the Control group (118±114ml) (P<0.01). PWVcf was higher in the SARS-CoV-2 group (5.83±0.62m/s) compared with the Control group (5.17±0.66m/s) (P<0.01). Conclusions: Significantly lower systemic vascular function and higher arterial stiffness are evident weeks after testing positive for SARS-CoV-2 among young adults compared to controls.

scholarly journals Racial disparities in cardiovascular disease risk: mechanisms of vascular dysfunction

2019 ◽  
Vol 317 (4) ◽  
pp. H777-H789 ◽  
Author(s):  
R. Matthew Brothers ◽  
Paul J. Fadel ◽  
David M. Keller
Keyword(s):  
Cardiovascular Disease ◽  
Vascular Function ◽  
Disease Risk ◽  
Vascular Dysfunction ◽  
Cardiovascular Disease Risk ◽  
The United States ◽  
Future Research ◽  
Therapeutic Approaches ◽  
Contributing Factors ◽  
Cvd Risk

Cardiovascular disease (CVD) accounts for a third of all deaths in the United States making it the leading cause of morbidity and mortality. Although CVD affects individuals of all races/ethnicities, the prevalence of CVD is highest in non-Hispanic black (BL) individuals relative to other populations. The mechanism(s) responsible for elevated CVD risk in the BL population remains incompletely understood. However, impaired vascular vasodilator capacity and exaggerated vascular vasoconstrictor responsiveness are likely contributing factors, both of which are present even in young, otherwise healthy BL individuals. Within this review, we highlight some historical and recent data, collected from our laboratories, of impaired vascular function, in terms of reduced vasodilator capacity and heightened vasoconstrictor responsiveness, in the peripheral and cerebral circulations in BL individuals. We provide data that such impairments may be related to elevated oxidative stress and subsequent reduction in nitric oxide bioavailability. In addition, divergent mechanisms of impaired vasodilatory capacity between BL men and women are discussed. Finally, we propose several directions where future research is needed to fill in knowledge gaps, which will allow for better understanding of the mechanisms contributing to impaired vascular function in this population. Ultimately, this information will allow for better lifestyle and therapeutic approaches to be implemented in an effort to minimize the increased CVD burden in the BL population.

Reactivity of the aorta and mesenteric resistance arteries from the obese spontaneously hypertensive rat: effects of glitazones

2011 ◽  
Vol 301 (4) ◽  
pp. H1319-H1330 ◽  
Author(s):  
Yolanda Mendizábal ◽  
Silvia Llorens ◽  
Eduardo Nava
Keyword(s):  
Vascular Function ◽  
Spontaneously Hypertensive Rat ◽  
Oral Treatment ◽  
Resistance Arteries ◽  
Response Curves ◽  
Spontaneously Hypertensive ◽  
Beneficial Effects ◽  
Hypertensive Rat ◽  
And Control ◽  
Endothelial Nitric Oxide

The obese spontaneously hypertensive rat (SHROB) is a model of metabolic syndrome in which, to our knowledge, vascular function has never been studied. The actions of insulin sensitizers (glitazones) on vascular function have not been analyzed either. Our purpose was to characterize microvascular and macrovascular responses of the SHROB and to study the effects of glitazones on these responses. The reactivity of mesenteric resistance arteries (MRAs) and the aorta from SHROBs and control rats to cumulative concentrations of phenylephrine, ACh, and sodium nitroprusside (SNP) was myographically analyzed. Some animals were orally treated with rosiglitazone (3 mg·kg−1·day−1, 3 wk), and myography was performed. Phenylephrine, ACh, and SNP dose-response curves were impaired to different extents in arteries of SHROBs. Incubation with N-nitro-l-arginine methyl ester caused little effects on phenylephrine and ACh curves in MRAs but enhanced phenylephrine contractions and abolished ACh-induced relaxations of aortae. Incubation with indomethacin reduced phenylephrine reactivity and improved ACh-induced relaxations of all vessels studied. NS-398 and tempol increased relaxations to ACh of MRAs. Incubation with pioglitazone or rosiglitazone (both 10−5 M) or oral treatment with rosiglitazone improved, to different extents, ACh and SNP curves in all vessels. Glitazone incubation diminished aortic ACh sensitivity. The release of thromboxane A2 and PGI2 metabolites (thromboxane B2 and 6-keto-PGF1α) was analyzed. ACh increased the MRA release of thromboxane B2 from SHROBs but not control rats, and the former was prevented by rosiglitazone coincubation. In contrast, in aortae, ACh failed to alter the release of metabolites, and rosiglitazone treatment increased that of 6-keto-PGF1α. Thus, SHROBs displayed microvascular and macrovascular dysfunction. MRAs, but not aortae, of SHROBs revealed an impaired endothelial nitric oxide pathway, whereas both, but especially MRAs, displayed an impaired cyclooxygenase pathway. Glitazones elicited beneficial effects on macrovascular and, especially, microvascular function of SHROBs.

The spontaneously hypertensive rat Y chromosome produces an early testosterone rise in normotensive rats

1994 ◽  
Vol 12 (7) ◽  
pp. 769???774 ◽  
Author(s):  
Daniel L. Ely ◽  
Jessica Falvo ◽  
Gail Dunphy ◽  
Ann Caplea ◽  
Ron Salisbury ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat
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