Studies on the pathophysiology of hypertension in the elderly.

This thesis examines two of the most important issues in the pathophysiology of hypertension in the elderly, disordered cardiovascular neural control and raised peripheral vascular resistance, in clinical studies of hypertensive and normotensive subjects aged over sixty years. Hypertension in elderly subjects is associated with reduced baroreceptor-cardiac reflex sensitivity irrespective of the method used to quantify the reflex. There is no difference in baroreceptor-cardiac reflex sensitivity between elderly subjects with combined systolic-diastolic hypertension and isolated systolic hypertension. Beyond the age of sixty years, baroreflex sensitivity is independently related to the level of systolic blood pressure but not to age. Subjects with isolated systolic hypertension have a greater fall in blood pressure with passive tilt than normotensives despite a greater rise in forearm vascular resistance. Hypertension in elderly subjects is associated with an increased media:lumen ratio in subcutaneous resistance arteries which principally relates to the prevailing level of pulse pressure, particularly when measured by 24-hour ambulatory monitoring. However, there are no differences with hypertension in the contractile behaviour of vascular smooth muscle or in the endothelium-dependent and independent relaxation responses of such resistance arteries. The sympathetic baroreceptor-vascular response is not correlated with the changes observed in the structure of the effector mechanism of the reflex, the resistance artery. However, blood pressure changes with orthostasis are negatively correlated with baroreceptor-cardiac reflex sensitivity, suggesting an aetiological link between hypertension and the postural hypotension with which it is often associated. In conclusion, hypertension in the elderly is associated with reduced baroreflex sensitivity, an impaired blood pressure response to orthostasis and increased resistance artery media:lumen ratio, but no differences in endothelial or vascular smooth muscle function. These findings should help clarify some of the pathophysiological issues in hypertension in the elderly, and guide our approach to the treatment of this common and clinically important condition.