The effect of mirthful laughter on the human cardiovascular system

Med Hypotheses. 2009 Nov;73(5):636-9. doi: 10.1016/j.mehy.2009.02.044. Epub 2009 May 27.


It has become increasingly recognized and more widely acknowledged during the past several decades, that a complex relationship exists between behavior associated with emotion and the human cardiovascular (CV) system. Early studies focused on the interplay between negative emotions and elevated CV risk, an effect that has in large part been attributed to increased adrenergic activity. Thus, a variety of adverse CV effects ranging from sudden cardiac death triggered by natural disasters such as earthquakes to transient myocardial stunning resulting from heightened sympathetic overload have been identified in response to acute emotional distress. In fact, the biologic interplay between emotion and CV health has been greatly enhanced through studies of the vascular endothelium. As the largest organ in humans, the inner blood vessel lining serves as a conduit for the transfer of blood cells, lipids and various nutrients across the lumen to neighboring tissues. Healthy endothelial cells secrete vasoactive chemicals, most notably endothelial-derived relaxing factor or nitric oxide (NO), that effects smooth muscle relaxation and vessel dilation via a cyclic guanosine monophosphate (cGMP) dependent protein kinase signaling pathway. In addition, endothelial derived NO may reduce vascular inflammation by attenuating or inhibiting leukocyte adhesion and subendothelial transmigration as well as decreasing platelet activation via cGMP mediated pathways. Taken together, studying the endothelium provides an exceptional opportunity to advance our understanding of the potentially important interrelationship between emotions and the vasculature. Premised on the identification of physiological and biochemical correlates, the former was demonstrated after intracoronary administration of acetylcholine yielded paradoxical endothelial vasoconstriction in response to mental stress exercises. More recently, the brachial artery reactivity test (BART) has permitted endothelial function to be assessed in a non-invasive manner. In addition to traditional CV risk factors, exposure to negative emotions including mental stress and depression have been associated with reduced endothelial vasoreactivity as measured by BART. Whether mirthful laughter has the opposite effect garnered consideration following the discovery that mu3 opiate receptors were expressed in the vascular endothelium. Because mirthful laughter induces the release of beta-endorphins which in turn have high affinity for mu3 opiate receptors, we hypothesize that such positive emotions lead to the direct release of NO and associated biological consequences. Indeed, our studies have demonstrated opposing effects on endothelial vasoreactivity between those previously established (e.g., mental stress induced by negative visual and/or auditory stimuli) and those induced after mirthful laughter, thereby providing a potential mechanistic link between positive emotions and beneficial effects on the vasculature. This article reviews the relevant physiology and comments on the potentially wider clinical implications in the integration of this process to improve vascular health.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cardiovascular Physiological Phenomena*
  • Cyclic GMP / physiology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiology
  • Humans
  • Laughter*
  • Models, Theoretical
  • Nitric Oxide / physiology
  • Protein Kinases / metabolism
  • Signal Transduction


  • Nitric Oxide
  • Protein Kinases
  • Cyclic GMP