Influence of left ventricular dimensions on β – adrenergic- induced cardiac remodeling in male spontaneously hypertensive rats

dc.contributor.authorTartibu, Linda Katanda
dc.date.accessioned2023-01-25T07:30:33Z
dc.date.available2023-01-25T07:30:33Z
dc.date.issued2022
dc.descriptionA dissertation submitted in fulfilment of the requirements for the degree of Master of Science in Medicine (Physiology) to the Faculty of Health Sciences, School of Pathology, University of the Witwatersrand, Johannesburg, 2022
dc.description.abstractHeart failure progression in hypertension is characterised by compensated left ventricular hypertrophy (LVH) which may progress to cardiac dilation. Adrenergic activation is another process in the transition to cardiac dilation. Regression of LVH following antihypertensive therapy ameliorates the prognosis of heart failure. However, impact of LVH regression on cardiac remodelling following adrenergic activation is unknown. The aim of the study was to determine the effect of LVH regression on ß-adrenergic-induced cardiac remodelling in male spontaneously hypertensive rats (SHRs). One-month-old male SHRs (21) and normotensive rats (8) were used in the study. During the first 6 months, SHRs were untreated, treated with: captopril (an angiotensin-converting enzyme inhibitor) or with hydralazine (a non-specific vasodilator). Normotensives were untreated. At 7 months, anti-hypertensive treatments were stopped and rats in the four groups received a daily isoproterenol (beta-adrenergic agonist) injection for 5 months. Blood pressure was measured every two weeks. Echocardiography was performed at 7 and 12 months of age. At 7 months, systolic blood pressure (SBP) was significantly higher in the untreated hypertensive group compared to the other groups. Ventricular wall thickness in diastole (WTd), relative wall thickness (RWT) and calculated left ventricular mass (LVMc) were significantly greater in untreated hypertensive group compared to the other groups. Ventricular functions were similar between the four groups. At 12 months, SBP was significantly higher in the hypertensive groups compared to the normotensive group. At 12 months compared to 7 months, WTd and the ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e’ filling index) were significantly increased in the hypertensive group. At 12 months, WTd, RWT and LVMc were significantly greater in the hypertensive group compared to the normotensive group and the hypertensive group previously treated with captopril. Endocardial fractional shortening and E/e’ filling index were significantly greater in the hypertensive group compared to the normotensive group. Left ventricular dimensions and functions were similar between hypertensive rats untreated and hypertensive rats previously treated with hydralazine. At 7 months, hypertensive rats developed concentric LVH without systolic or diastolic dysfunction, suggesting a compensation process. Both antihypertensive drugs reduced LVH to a similar extent as normotensive rats. At 12 months, hypertensive rats developed eccentric LVH with signs of diastolic dysfunction, suggesting a progression to cardiac dilation with ß-adrenergic-receptor activation. The regression of LVH with a non-specific vasodilator before ß-adrenergic-receptor activation did not hamper the development of eccentric LVH in hypertensive rats. However, the regression of LVH with an angiotensin-converting enzyme inhibitor before receptor activation prevented eccentric LVH in hypertensive rats to a similar extent than in normotensive rats. In conclusion, activation of the renin-angiotensin-aldosterone system independent of blood pressure may be detrimental in the development of ß-adrenergic-induced cardiac remodelling
dc.description.librarianNG (2023)
dc.facultyFaculty of Health Sciences
dc.identifier.urihttps://hdl.handle.net/10539/34225
dc.language.isoen
dc.schoolSchool of Pathology
dc.titleInfluence of left ventricular dimensions on β – adrenergic- induced cardiac remodeling in male spontaneously hypertensive rats
dc.typeDissertation
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