LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Endothelial Dysfunction and Phenylephrine-Induced Hypocontractility Occurs in Mesenteric Resistance Arteries Prior to the Onset of Alzheimer's Disease in Mice

Photo from wikipedia

Alzheimer’s Disease (AD) is the most common form of dementia and a major cause of disability and death among the older population. In addition, Cardiovascular dieseases (CVDs) and their risk… Click to show full abstract

Alzheimer’s Disease (AD) is the most common form of dementia and a major cause of disability and death among the older population. In addition, Cardiovascular dieseases (CVDs) and their risk factors are associated with an increased risk of the progression of AD and cognitive impairment. Despite this, studying the combination of these diseases constitutes a clinical challenge, and investigations to understand the mechanistic pathways for the cause-effect and/or shared pathology between them remains an active area of research. One form of AD, familial AD, is linked with an early onset AD (EOAD) pathology (<65years) that manifests through pathogenic mutations in the genes encoding the amyloid precursor protein (APP) and the g-secretase complex enzymes presenilin (PSEN)1 and PSEN2 which result in the increased production of central amyloid β (Aβ) peptides. There is increasing evidence that amyloid deposition in peripheral vessels has powerful structural effects in CVDs which, in turn, increase the risk of cognitive decline later in life. With this premise, we hypothesized that vascular dysfunction would be observed in the resistance arteries prior to the development of EOAD regardless of sex. To test the hypothesis, mesenteric resistance arteries (MRA) were isolated from male and female early onset AD mice (B6.CApptm1Dbo Tg(APPswe, PSEN1dE9)85Dbo/Mmjax) prior to (9 weeks of age) and after the onset of AD (28 weeks of age). Vascular function was evaluated using wire myography and concentration-effect curves to acetylcholine, phenylephrine and to U46619, a thromboxane A2 analog, were performed. Data were analyzed using non-linear regression analysis and maximum response (Rmax) analyzed by Student t test (p<0.05*). Arteries from 9-week-old AD mice showed impaired acetylcholine-induced relaxation and phenylephrine-induced hypocontractility for males [Rmax: control 11.72±0.9 vs. AD 7.70±0.8*, n=3-4]. Females presented a similar tendency of phenylephrine-induced hypocontractility. However, a “catch-up phenomenon” was observed and resulted in phenylephrine-induced hypercontractility in arteries from 28-weeks-old AD mice Males [Rmax: control 9.34±1.3 vs. AD 14.5±0.4*, n=3-5] and Females [Rmax: control 10.4± 2.8 vs. AD 13.8±1.5mN, n=3-4]. The same hypercontractility profile was observed in the arteries isolated from 28-weeks-old AD mice for U46619 agonist in both males [Rmax: control 12.4±1.5 vs. AD 15.6± 0.6*mN, n=3-5] and the females [Rmax: control 9.3± 1.7 vs. AD 14.3±1.9mN, n=3-4]. Overall, our data suggest that vascular dysfunction, which may lead to disrupted blood flow, nutrients and oxygen delivery to the brain, could contribute to the genesis and maintenance of AD. R00GM118885, R01HL149762, R00HL151889, and NHLBI (R00HL151889) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Keywords: phenylephrine induced; pathology; physiology; resistance arteries; mice

Journal Title: Physiology
Year Published: 2023

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.