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Age-associated decrease in histamine-induced vasodilation may be due to reduction of cyclic GMP formation.

H Moritoki1, A Tanioka, Y Maeshiba

  • 1Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.

British Journal of Pharmacology
|December 1, 1988
PubMed
Summary
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Aging significantly impairs histamine-induced arterial dilation and cyclic GMP production in rats. Endothelial function and guanylate cyclase activity decrease with age, reducing vascular responsiveness.

Area of Science:

  • Cardiovascular Physiology
  • Aging Research
  • Pharmacology

Background:

  • Histamine induces arterial vasodilation via H1-receptors, dependent on endothelial factors.
  • Cyclic guanosine monophosphate (cGMP) plays a crucial role in vascular smooth muscle relaxation.

Purpose of the Study:

  • To investigate the impact of aging on histamine-induced vasodilation and cyclic GMP production in rat thoracic aorta.
  • To elucidate the age-related mechanisms underlying reduced vascular responsiveness to histamine.

Main Methods:

  • Experiments were conducted on rat thoracic aortas of varying ages (3 weeks to 130 weeks).
  • Histamine-induced relaxation and cyclic GMP levels were measured.
  • The effects of endothelium removal, nitroprusside, and 8-bromo cyclic GMP were assessed.

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Main Results:

  • Histamine-induced vasodilation and cyclic GMP production were highest in young rats and significantly decreased with age.
  • Endothelium removal abolished histamine-induced cyclic GMP increase.
  • Age-related attenuation was observed for nitroprusside and 8-bromo cyclic GMP dilator effects.

Conclusions:

  • Aging impairs endothelial production of endothelium-derived relaxing factor (EDRF), reducing cyclic GMP synthesis.
  • Decreased vascular response to histamine in aging is attributed to reduced endothelial function and guanylate cyclase activity.
  • Alterations in cyclic GMP-dependent protein kinase may also contribute to age-related vascular changes.