Leandro Bueno Bergantin and Afonso Caricati-Neto
Federal University of S├?┬úo Paulo, Brazil
Posters & Accepted Abstracts: J Tissue Sci Eng
The hypothesis of the so-called calcium paradox phenomenon in the sympathetic neurotransmission has its origin in experiments done in models of neurotransmission since 1970├ó┬?┬?s. Historically, calcium paradox originated several clinical studies reporting that acute and chronic administration of L-type Ca2+ Channel Blockers (CCBs), drugs largely used for antihypertensive therapy such as verapamil and nifedipine produces reduction in peripheral vascular resistance and arterial pressure, associated with a paradoxical sympathetic hyperactivity. Despite this sympathetic hyperactivity has been initially attributed to adjust reflex of arterial pressure, the cellular and molecular mechanisms involved in this paradoxical effect of the L-type CCBs remained unclear for four decades. Also, experimental studies using isolated tissues richly innervated by sympathetic nerves showed that neurogenic responses were completely inhibited by L-type CCBs in high concentrations but paradoxically potentiated in low concentrations, characterized as a calcium paradox phenomenon. We discovered in 2013 that this paradoxical increase in sympathetic activity produced by L-type CCBs is due to Ca2+/cAMP interaction. Then, the pharmacological manipulation of this interaction could represent a potential cardiovascular risk for hypertensive patients due to increase of sympathetic hyperactivity. In contrast, this pharmacological manipulation could be a new therapeutic strategy for increasing neurotransmission in psychiatric disorders such as depression and producing neuroprotection in the neurodegenerative diseases such as Alzheimer├ó┬?┬?s and Parkinson├ó┬?┬?s diseases.
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