Venous physiology of aldosterone and bradykinin in health and chronic heart failure

In this thesis I examined vascular physiology, with an emphasis on venous physiology, of two important neuro-hormones, aldosterone and bradykinin, in health and in chronic heart failure. Capacitance venous tone governs the volume of blood in the peripheral vs. central circulation and thus indirectly influences cardiac output. Mechanisms that control venous tone in health and in heart failure are poorly understood. Chapter 1 discusses the importance of venous physiology in governing cardiac output in health and heart failure. The significance of pressure volume relationships, rather than pressure flow relationships in capacitance veins is explained. The physiological measures and the terms used to describing changes in parameters are defined. Chapter 2 is a literature review of pharmacology and physiology of aldosterone and bradykinin, with an emphasis on vascular physiology in health and in chronic heart failure. Chapter 3 describes in detail our methods of assessing both resistance and capacitance vascular functions. It examines changes to vasculature with a semi-supine posture, relationship between arterial flow and venous capacitance, and compares two established techniques in assessing capacitance veins. Chapter 4, 5 and 6 examines in detail the effects of aldosterone and bradykinin on human forearm vasculature, and differences in vascular responses between states of health and heart failure are discussed. The important new findings of this thesis are: 1. In physiological concentrations, aldosterone does not acutely alter vascular physiology in health. 2. In contrast, in treated heart failure aldosterone decreases blood flow in resistance vessels but not in capacitance vessels 3. Bradylcinin modulates venous capacitance in health via its Type 2 receptor. However, bradykinin does not contribute to basal vascular tone in health 4. In angiotensin-converting-enzyme-inhibitor-treated heart failure, bradykinin contributes to basal venous tone. In contrast, bradykinin does not contribute to venous tone in heart failure treated with angiotensin II receptor antagonists. 5. In mild to moderate heart failure bradykinin effects are mediated via the Type 2 Bradykinin receptor. 6. A paradoxical enhanced venodilatation was discovered in heart failure patients on both aspirin and angiotensin converting enzyme inhibitors, in comparison to those only on the latter.