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Sex-related decrease in [Ca2+]i signaling and Ca2+-dependent contraction in inferior vena cava of female rat
1Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Summary
Female rats exhibit reduced venous function, with lower intracellular calcium ([Ca(2+)](i)) sensitivity, potentially explaining the higher incidence of varicose veins in women. This study highlights sex-specific differences in venous contraction mechanisms.
Area of Science:
- Physiology
- Vascular Biology
- Calcium Signaling
Background:
- Sex differences in varicose vein incidence are noted, but underlying venous mechanisms remain unclear.
- Intracellular free calcium ([Ca(2+)](i)) signaling and Ca(2+)-dependent contraction are critical for venous function.
- This study investigates potential sex-related differences in venous function and calcium handling.
Purpose of the Study:
- To investigate sex-specific differences in inferior vena cava (IVC) function in Sprague-Dawley rats.
- To determine if sex differences exist in intracellular calcium ([Ca(2+)](i)) signaling and Ca(2+)-dependent venous contraction.
- To explore the role of calcium influx and myofilament sensitivity in sex-based variations of venous contractility.
Main Methods:
- Isometric contraction and intracellular calcium ([Ca(2+)](i)) levels were simultaneously measured in male and female rat IVC segments using fura-2 and spectrofluorometry.
- Vascular smooth muscle contraction was stimulated using phenylephrine (PHE) and potassium chloride (KCl) under varying extracellular calcium ([Ca(2+)](e)) conditions.
- Ca(2+)-dependent contraction and Ca(2+)-contraction relationships were analyzed to assess venous function and myofilament sensitivity.
Main Results:
- Phenylephrine (PHE)-induced contraction was significantly reduced in female IVC, despite similar intracellular calcium ([Ca(2+)](i)) levels compared to males.
- KCl-induced contraction and calcium ([Ca(2+)](i)) influx were reduced in female IVC, suggesting impaired Ca(2+) entry via voltage-gated channels.
- While Ca(2+) influx differed, the [Ca(2+)](i)-contraction relationship revealed reduced myofilament sensitivity in female veins, particularly with PHE stimulation.
Conclusions:
- Female rat veins exhibit reduced contractility and impaired Ca(2+) handling, characterized by decreased Ca(2+) influx and lower myofilament sensitivity.
- These sex-specific functional deficits in venous smooth muscle may contribute to venous dilation and increased susceptibility to varicose veins in females.
- Understanding these sex differences in venous physiology is crucial for elucidating the pathophysiology of varicose veins.
