RuBPY decreases intracellular calcium by decreasing influx and increasing storage

• Published in: Clinical and experimental pharmacology & physiology 2022-07, Vol.49 (7), p.759-766
• Main Authors: Pereira, Amanda de Carvalho, Araújo, Alice Valença, Paulo, Michele, Silva, Roberto Santana, Bendhack, Lusiane Maria
• Format: Article
• Language: English
• Subjects: Animals; Aorta; Arteries; Blood pressure; Ca2+-transporting ATPase; Caffeine; Calcium; Calcium (intracellular); Calcium (reticular); Calcium - metabolism; Calcium influx; Calcium ions; Calcium mobilization; calcium signalling; capacitive Ca2+ influx; Confocal microscopy; Cyclic GMP; Heart rate; Intracellular; Muscle contraction; Muscles; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Nitrogen dioxide; Phenylephrine; Phenylephrine - pharmacology; Potassium chloride; Pressure reduction; Rats; Ruthenium; Ruthenium - pharmacology; Ruthenium compounds; Sarcoplasmic reticulum; SERCA; Smooth muscle; Thapsigargin; Vasodilation
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.13652

cis‐[Ru(bpy)2(py)NO2](PF6) (RuBPY) is a ruthenium complex nitric oxide (NO) donor that presents a nitrite in its moiety and has been shown to induce vasodilation in various arteries, as well as arterial pressure reduction with no changes in heart rate. Because vascular tone is highly dependent on the cytosolic calcium concentration ([Ca2+]c), the current study aimed to investigate the effects of RuBPY on the intracellular mobilization of calcium stores of rat aortic vascular smooth muscle cells. Vascular reactivity experiments were performed in isolated aortic rings that were contracted with a high concentration of KCl or phenylephrine (Phe). Moreover, primary cultured vascular smooth muscle cells were used to measure [Ca2+]c by confocal microscopy. The NO donor RuBPY decreased the [Ca2+]c and reduced KCl and Phe‐induced contractile responses. The selective inhibitor of sarco‐endoplasmic Ca‐ATPase (SERCA) with thapsigargin impaired the effect of RuBPY on Phe‐induced contractile response. RuBPY also reduced caffeine‐induced contraction, and the contraction dependent on the capacitive Ca2+ influx. Therefore, our results suggest that NO released from RuBPY decreased [Ca2+]c by calcium influx blockade and activation of guanylyl‐cyclase‐cGMP‐GK pathway. These results indicate that RuBPY increases Ca2+ storage in the sarcoplasmic reticulum by SERCA activation and also by capacitive Ca2+ influx inhibition, which is dependent on the intracellular release of nitric oxide from this compound.