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

Doctoral thesis English OPEN
Schmitt, Matthias
  • Subject: R1
    mesheuropmc: hormones, hormone substitutes, and hormone antagonists

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.
  • References (92)
    92 references, page 1 of 10

    M e th o d s ...............................................................................................161 Haemodynamic measurements.................................................................................. 162 Drugs...........................................................................................................................164 Protocol / Surgical preparation................................................................................. 164 5.3.

    Discussion........................................................................................... 177 The effect of ANP and BNP on large conduit arteries..............................................177 CNP - a vasoactive NP?..............................................................................................178 Effects of Basal ANP plasma levelson large artery distensibility............................ 179 Clinical considerations................................................................................................ 180 Limitations.................................................................................................................. 180 5.6.

    CHAPTER 6 - THE EFFECTS OF NOVEL NATRIURETIC PEPTIDES (NNP / DNP) ON ISOLATED RINGS OF RABBIT AORTA; COMPARISON TO ANP AND D N P ........................................................................................................ 183 6.1.

    M eth o d s ................................................................................................ 184 Isometric Tension Recordings................................................................................... 185 Drugs and Chemicals................................................................................................. 187 Statistical analysis....................................................................................................... 188 R esults.................................................................................................. 188 Comparative ANP, DNP, NNP dose response study.................................................188 The Effects of Nitric Oxide (NO) in NNP induced vasorelaxation.......................... 190 The Effects of Prostaglandins in NNP-induced vasorelaxation.............................. 191 The Effects of sGC in NNP-induced vasorelaxation.................................................192 The Effects of NPRa-NNP interaction on vascular smooth muscle tone................193 The Effects of NPRc-NNP interaction on vascular smooth muscle tone ...............196 6.4.

    393. Mills RM, LeJemtel TH, Horton DP et al. Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. Natrecor Study Group. J Am Coll Cardiol 1999;34:155-62.

    394. Colucci WS, Elkayam U, Horton DP et al. Intravenous nesiritide, a natriuretic peptide, in the treatment o f decompensated congestive heart failure. Nesiritide Study Group. N Engl J Med 2000;343:246-53.

    395. Burger AJ, Elkayam U, Neibaur MT et al. Comparison of the occurrence of ventricular arrhythmias in patients with acutely decompensated congestive heart failure receiving dobutamine versus nesiritide therapy. Am J Cardiol 2001;88:35-9.

    396. Burger AJ, Horton DP, LeJemtel T et al. Effect of nesiritide (B-type natriuretic peptide) and dobutamine on ventricular arrhythmias in the treatment of patients with acutely decompensated congestive heart failure: the PRECEDENT study. Am Heart J 2002; 144:1102-8.

    398. Yoshimura M, Yasue H, Morita E et al. Hemodynamic, renal, and hormonal responses to brain natriuretic peptide infusion in patients with congestive heart failure. Circulation 1991;84:1581-8.

    399. Abraham WT, Lowes BD, Ferguson DA et al. Systemic hemodynamic, neurohormonal, and renal effects of a steady- state infusion of human brain natriuretic peptide in patients with hemodynamically decompensated heart failure. J Card Fail 1998;4:37-44.

  • Metrics
    0
    views in OpenAIRE
    0
    views in local repository
    22
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    Online Research @ Cardiff - IRUS-UK 0 22
Share - Bookmark