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Mevalonate availability and cardiovascular functions

J B Roullet1, H Xue, A S Pappu

  • 1Division of Nephrology, Hypertension and Clinical Pharmacology, Oregon Health Sciences University, Portland 97201.

Proceedings of the National Academy of Sciences of the United States of America
|December 15, 1993
PubMed
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Mevalonate, a cholesterol precursor, influences blood pressure (BP) and vascular tone. Altering mevalonate levels impacts BP and blood vessel reactivity, suggesting a role beyond cholesterol in cardiovascular health.

Area of Science:

  • Biochemistry
  • Cardiovascular Physiology
  • Metabolic Disorders

Background:

  • The relationship between cholesterol metabolism disorders and elevated blood pressure (BP) is not well-defined.
  • Mevalonate, a key metabolic precursor in cholesterol synthesis, is investigated for its role in vascular tone and BP regulation.

Purpose of the Study:

  • To investigate the direct impact of mevalonate availability on blood pressure and vascular reactivity.
  • To determine if metabolites of the mevalonate pathway, independent of cholesterol, influence cardiovascular hemodynamics.

Main Methods:

  • In vivo, ex vivo, and in vitro studies were performed using normotensive and hypertensive rats.
  • Mevalonate was administered to increase its availability, while lovastatin was used to inhibit its production.

Related Experiment Videos

  • Vascular reactivity was assessed using norepinephrine and various relaxing factors.

    • Main Results:

    • Exogenous mevalonate decreased BP without altering plasma cholesterol levels.
    • Mevalonate attenuated aortic reactivity to norepinephrine and enhanced responses to relaxing factors.
    • Lovastatin increased BP, enhanced norepinephrine reactivity, and impaired vascular relaxations, independent of vascular cholesterol content.

    Conclusions:

    • Mevalonate availability is an unrecognized factor in regulating vascular tone and blood pressure.
    • Mevalonate pathway metabolites, not just cholesterol, may control vascular function and cardiovascular hemodynamics.
    • Inhibiting mevalonate production for cholesterol lowering might adversely affect blood pressure control.