Altered mitochondrial function, capacitative calcium entry and contractions in the aorta of hypertensive rats
| Autor: | Juan Alberto Arranz-Tagarro, J. Fernando Padín, Juan P. Velasco-Martín, Diego Castro Musial, Guilherme Henrique Souza Bomfim, Aron Jurkiewicz, Iago Méndez-López, Javier Regadera, Neide H. Jurkiewicz, Antonio G. García |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Vascular smooth muscle Physiology chemistry.chemical_element Calcium Endoplasmic Reticulum Rats Inbred WKY Muscle Smooth Vascular 03 medical and health sciences Spontaneously hypertensive rat Rats Inbred SHR Internal medicine Internal Medicine medicine Animals Aorta Calcium metabolism Voltage-dependent calcium channel business.industry ORAI1 Endoplasmic reticulum STIM1 Anatomy Mitochondria Rats 030104 developmental biology Endocrinology chemistry Hypertension Calcium Channels Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of Hypertension. 35:1594-1608 |
| ISSN: | 0263-6352 |
| DOI: | 10.1097/hjh.0000000000001360 |
| Popis: | Objective It has been suggested that Ca entry through store-operated Ca channels (SOCs) is regulated by a dynamic interplay between the endoplasmic reticulum Ca stores and the mitochondria. These relationships drive the activation and inactivation of SOCs, yet it remains unclear whether this regulation of SOCs by mitochondria is altered in the aorta of spontaneously hypertensive rats (SHRs). Methods We performed a thorough study of the mitochondrial membrane potential, the ability of mitochondria to deal with cytosolic Ca, capacitative Ca entry (CCE), and stromal interaction molecule 1 (STIM1) and calcium release-activated calcium modulator 1 (orai1) protein expression, as well as the contractile capacity of aortic rings, in normotensive Wistar Kyoto rats (WKYs) and SHRs. Results Changes were observed in aortic tissue and cultured vascular smooth muscle cells isolated from SHRs relative to WKYs, including more depolarized mitochondria, stronger CCE upon the addition of Ca, larger cytosolic Ca transients (cytosolic Ca concentration) or aortic ring contraction elicited by endoplasmic reticulum depletion and a significant increase in STIM1 protein expression but not of orai1. Conclusion These results suggest that the impaired Ca buffering capacity of partially depolarized mitochondria dysregulates CCE, leading to overfilling of the endoplasmic reticulum Ca store through enhanced STIM1/orai1 interactions and an increase in aorta contractions in SHRs. Thus, understanding the implications of the alterations to STIM1/orai1, and their relationship to mitochondria, may aid drug development and therapeutic strategies to treat hypertension, as well as its long-term sequelae in poorly controlled patients. |
| Databáze: | OpenAIRE |
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