Hypertension is the leading modifiable cause of premature death worldwide. Some hypertensive individuals develop left ventricular (LV) hypertrophy (LVH) and myocardial fibrosis, increasing cardiovascular morbidity and mortality, whereas some hypertensive individuals have normal LV structure and function. The sympathetic nervous system (SNS) and immune system are known to play a role in hypertension and cardiac remodelling; however, it remains unknown whether inflammation causes sympathetic overactivation, or if elevated sympathetic nerve activity (SNA) induces inflammation in hypertension. This thesis hypothesised that inflammation would precede sympathetic overactivation in the development of cardiac remodelling. Temporal changes in lumbar SNA and inflammatory markers in spontaneously hypertensive rats (SHRs) were observed from 10-weeks-old to 15-weeks-old, with circulating IL-18 found to be a significant predictor of LVH. However, due to issues with data collection, lumbar SNA data was inconclusive. This thesis also aimed to identify whether resting SNA or SNA reactivity was associated with cardiac remodelling in humans. Resting SNA was found to predict concentric cardiac remodelling, and SNA reactivity was a predictor of cardiac fibrosis in people with and without hypertension. Resting SNA was also found to predict circulating IL-18, confirming a link between SNA and inflammation, although no inflammatory markers were associated with cardiac remodelling. However, a type III collagen synthesis marker, amino-terminal propeptide of procollagen type III (PIIINP) was found to predict LVH, but no markers predicted myocardial fibrosis. Additionally, stress induced increases in SNA were found to be sustained in recovery in hypertensive but not normotensive individuals, having implications for increased cardiovascular risk. Finally, hypertensive individuals had an increased rise in pro-inflammatory markers following exercise, with change in IL-10 being an independent predictor of ECV. Overall, this thesis has shown resting SNA and SNA reactivity predict cardiac remodelling and circulating IL-18, IL-10 and PIIINP may be potential biomarkers to predict cardiac remodelling.
Investigating the link between sympathetic nerve activation and inflammation in the progression of hypertensive heart disease
Blythe, H. C. (Author). 20 Jun 2023
Student thesis: Doctoral Thesis › Doctor of Philosophy (PhD)