Calcium oscillations in human mesenteric vascular smooth muscle

Area of Science:

• Cardiovascular Physiology
• Vascular Biology
• Smooth Muscle Physiology

Background:

• Phenylephrine-induced intracellular calcium ([Ca2+]i) oscillations in vascular smooth muscle are well-documented in mammals.
• Such observations in human blood vessels have been challenging until recently.

Purpose of the Study:

• To report the first observation of adrenergically-stimulated [Ca2+]i oscillations in human mesenteric artery smooth muscle.
• To investigate the role of sarcoplasmic reticulum Ca2+ and IP3R in these oscillations.

Main Methods:

• Human mesenteric artery segments were mounted on a myograph and loaded with Fluo-4 AM.
• Confocal microscopy was used to observe PE-induced [Ca2+]i oscillations.
• Pharmacological agents (2-APB, CPA, nifedipine) were used to characterize the oscillations.

Main Results:

• PE induced [Ca2+]i oscillations that initiated and maintained vasoconstriction in human mesenteric arteries.
• Ultrastructural analysis revealed reduced plasma membrane-sarcoplasmic reticulum apposition in human tissues compared to animal models.
• 2-APB, CPA, and nifedipine generally reduced or inhibited oscillations and caused relaxation, with CPA showing limited relaxation effects.

Conclusions:

• This study provides the first evidence of PE-induced [Ca2+]i oscillations in human mesenteric artery smooth muscle.
• The findings suggest a potential involvement of sarcoplasmic reticulum Ca2+ and IP3R in maintaining these oscillations in human vasculature.
• Tissue health and reduced membrane-sarcoplasmic reticulum apposition may influence oscillation characteristics.