Endocrine and paracrine aspects of vascular control : the effects of natriuretic peptides on human capacitance in health and chronic heart failure

• Main Author: Schmitt, Matthias
• Published: Cardiff University 2004
• Subjects: 616.1
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.583434

The effects of natriuretic peptides on vascular control were investigated. In the major part of this thesis emphasis is placed on the effects of natriuretic peptides, in particular ANP, on regulation of regional vascular volume and venous tone in healthy volunteers (Chapter 3) and patients with chronic heart failure (Chapter 4). The second part of this thesis investigates the effects and mechanisms of action of ANP, BNP and CNP on large artery function in an ovine hind limb model (Chapter 5). Finally, the actions of the latest members of the natriuretic peptide family, namely DNP and NNP are investigated in vitro using rings of rabbit aorta in organ bath experiments (Chapter 6). The important new findings of this thesis are 1. ANP regulates regional vascular volume and venous tone over a wide range of physiological and pathophysiological plasma levels without affecting compliance. 2. Most importantly, basal ANP plasma levels contribute significantly to regulation of resting vascular tone. 3. The rank order of potency of NP in the forearm capacitance vasculature of patients with chronic heart failure is ANP BNP>CNP/Urodilatin. 4. Venous ANP responsiveness is preserved in patients with chronic heart failure despite marked impairment in the resistance vasculature. This preservation may be due to preserved venous endothelial function. 5. ANP acting locally modifies pulse wave velocity via the NPRa receptor. Neither CNP (acting via the NPRb receptor) nor cANF (acting via NPRc) elicit any immediate vasoactive effects. 6. Novel natriuretic peptide (NNP), a newly isolated NP from the venom of the green mamba snake (Dendroaspis angusepticus) has arterial vasorelaxant properties similar to those of ANP and DNP.