Alpha 1 adrenergic receptor function in senescent Fischer 344 rat aorta

Area of Science:

• Cardiovascular Physiology
• Aging Research
• Pharmacology

Background:

• Conflicting reports exist on alpha 1 adrenergic receptor-mediated blood vessel contraction during aging.
• Changes in alpha 1 receptor signal transduction mechanisms in aging vasculature are not well understood.

Purpose of the Study:

• To investigate the aging vascular alpha 1 receptor's capacity to stimulate inositol phosphate production.
• To assess the ability of the aging alpha 1 receptor pathway to elicit vascular contraction.

Main Methods:

• Aortic ring segments from mature (6-month) and senescent (24-month) Fischer 344 rats were used.
• Segments were incubated with [3H]myo-inositol and stimulated with norepinephrine (NE) in the presence of LiCl.
• Inositol phosphate accumulation and contraction in Ca++ free buffer were measured.

Main Results:

• Aortic rings from senescent rats showed significantly increased inositol phosphate accumulation in response to NE compared to mature rats.
• This increase in inositol phosphate was confirmed as an alpha 1 adrenergic receptor response.
• Aortic segments from senescent rats exhibited reduced contraction in Ca++ free buffer, indicating a deficiency in second messenger-mediated contraction.

Conclusions:

• Vascular alpha 1 receptor-mediated inositol phosphate formation is enhanced in aging Fischer 344 rats.
• Despite enhanced signaling, the contractile capacity of senescent arteries via second messenger pathways is impaired.
• This suggests a dissociation between alpha 1 receptor signal generation and functional vascular response during aging.