Aging Reduces L-Type Calcium Channel Current and the Vasodilatory Response of Small Mesenteric Arteries to Calcium

Sulayma A Albarwani1, Fathi Mansour1, Abdul Aleem Khan1

  • 1Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University Muscat, Oman.

Insights

Aging reduces the effectiveness of calcium channel blockers (CCBs) in mesenteric arteries. This decreased sensitivity is linked to lower L-type voltage-gated calcium channel (LTCC) current density in older rats.

Area of Science:

  • Cardiovascular Physiology
  • Aging Research
  • Pharmacology

Background:

  • Calcium channel blockers (CCBs) are crucial for managing cardiovascular diseases (CVD), with usage increasing in aging populations.
  • Aging is an independent risk factor for CVD, necessitating an understanding of its impact on drug efficacy.

Purpose of the Study:

  • To investigate how aging affects the sensitivity of small mesenteric arteries to L-type voltage-gated calcium channel (LTCC) blockers.
  • To determine if aging alters calcium current density in these arteries.

Main Methods:

  • Isometric tension measurements of third-order mesenteric arteries from young (2.5-3 months) and old (22-26 months) male F344 rats.
  • Cumulative concentration-response curves for nifedipine, verapamil, and diltiazem to assess artery relaxation.
  • Electrophysiological assessment of LTCC current density and Western blot analysis for Cav1.2 protein expression.

Main Results:

  • Older rats exhibited significantly reduced sensitivity (right-shifted IC50 values) to CCBs compared to younger rats.
  • Bay K 8644-induced increases in resting tension were diminished in arteries from old rats.
  • LTCC current density and Cav1.2 protein expression were significantly lower in arteries from old rats.

Conclusions:

  • Aging diminishes the vasodilatory response of small mesenteric arteries to CCBs.
  • Reduced LTCC current density, associated with decreased Cav1.2 protein expression, is a key factor contributing to this age-related decrease in CCB sensitivity.

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