Gender-dependent difference in cell calcium handling in VSMC isolated from SHR: the effect of angiotensin II.

Abstract

To investigate gender-dependent difference in the free cytosolic calcium concentration ([Ca2+ ]i ) response to angiotensin II (Ang II) in vascular smooth muscle cells (VSMC) isolated from spontaneously hypertensive rats (SHR). To further evaluate this gender-dependent difference by studying the role of thapsigargin-sensitive intracellular calcium stores and calcium influx in VSMC isolated from male and female SHR. Confluent primary cultures of VSMC isolated from male (n = 14) and female (n = 14) SHR aged 10 weeks were used in this study. [Ca2+ ]i was measured by image analysis of single myocytes loaded with Fura-2. [Ca2+ ]i response of VSMC to Ang II was measured in the presence and absence of extracellular Ca2+, to evaluate the influence of Ca2+ influx. To characterize inositol triphosphate (IP3 )-sensitive sarcoplasmic reticulum calcium stores, thapsigargin-sensitive calcium stores were measured in VSMC isolated from SHR of both genders. VSMC isolated from male SHR were characterized by an augmented [Ca2+ ]i response to angiotensin II in comparison with VSMC isolated from female SHR. Surprisingly, the thapsigargin-stimulated [Ca2+ ]i rise was found to be significantly greater in VSMC isolated from female SHR compared with VSMC isolated from male SHR. On the other hand, the gender-dependent difference in [Ca2+ ]i response to angiotensin II was abolished in the absence of extracellular calcium. We demonstrated in VSMC isolated from SHR of both genders that a greater [Ca2+ ]i response to angiotensin II in male than female VSMC is dependent on Ca2+ influx.