Vascular abnormalities of cerebral arteries and penetrating arterioles during hypertension and heart failure
| dc.contributor.author | Acosta, Crystal May | |
| dc.contributor.examiningcommittee | Hannila, Sari (Human Anatomy & Cell Science) | en_US |
| dc.contributor.examiningcommittee | Pierce, Grant (Physiology & Pathophysiology) | en_US |
| dc.contributor.examiningcommittee | Welsh, Don (University of Western Ontario) | en_US |
| dc.contributor.supervisor | Anderson, Hope (Pharmacology & Therapeutics) Anderson, Chris (Pharmacology & Therapeutics) | en_US |
| dc.date.accessioned | 2020-09-02T17:21:41Z | |
| dc.date.available | 2020-09-02T17:21:41Z | |
| dc.date.copyright | 2020-09-02 | |
| dc.date.issued | 2020 | en_US |
| dc.date.submitted | 2020-08-25T23:55:17Z | en_US |
| dc.date.submitted | 2020-09-02T15:58:38Z | en_US |
| dc.degree.discipline | Pharmacology and Therapeutics | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | Hypertension increases resistance to blood flow and compromises the vasculature. Chronically elevated blood pressure is antecedent to heart failure and both are associated with the development of cognitive decline and dementia. Thus, we sought to examine the cerebrovascular effects of hypertension alone and with predisposition for heart failure. Using pressurized cerebral vessels isolated from animals with genetic hypertension, we investigated structural, mechanical and functional properties by pressure myography. Structural and mechanical parameters were calculated using media and lumen dimensions measured at constant or incremental intraluminal pressures, respectively. Middle cerebral arteries (MCA) from spontaneously hypertensive heart failure (SHHF) rats underwent a combination of growth and remodeling, exhibited greater wall component stiffness and were less compliant. Studies suggest resveratrol may be beneficial for the treatment of hypertension. Therefore, we investigated the effects of resveratrol and two structural analogs on abnormal MCA. Vascular hypertrophy and wall component stiffness improved with oral doses (2.5 mg/kg/d) of resveratrol, pterostilbene and gnetol, albeit in the absence of blood pressure lowering. This indicates these stilbenoids act directly on the vascular wall. Findings in MCA led to further examination of downstream penetrating arterioles that regulate cerebral perfusion. SHHF penetrating arterioles exhibited eutrophic remodeling, increased stiffness and reduced compliance. Although eutrophic remodeling was similarly observed in spontaneously hypertensive rats (SHR), penetrating arterioles were less stiff and more compliant. Transmission electron microscopy revealed increased collagen deposition in arterioles from SHHF rats consistent with reduced compliance. Whereas, SHR arterioles had unchanged collagen/elastin ratio. Functional responses were evaluated using pharmacological agents that were bath applied to penetrating arterioles in increasing concentrations. Relaxation to glutamate/D-serine was reduced in SHHF rats but not in SHR. In contrast, acetylcholine-mediated relaxation was potentiated in SHR but maintained in SHHF rats. Interestingly, endothelium-independent relaxation to nitric oxide donor, sodium nitroprusside, resulted in constriction in both hypertensive strains. These findings suggest penetrating arterioles undergo some adaptations in hypertension, which are absent when there is a propensity for developing heart failure. Altogether, this is the first to identify and characterize the cerebrovascular abnormalities in MCA and penetrating arterioles in models of hypertension alone and with risk for heart failure. | en_US |
| dc.description.note | October 2020 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/34940 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Hypertension | en_US |
| dc.subject | Heart failure | en_US |
| dc.subject | Cerebral arteries and arterioles | en_US |
| dc.title | Vascular abnormalities of cerebral arteries and penetrating arterioles during hypertension and heart failure | en_US |
| dc.type | doctoral thesis | en_US |