Aldosterone is the most known mineralocorticoid hormone synthesized by the adrenal cortex. The genomic pathway displayed by aldosterone is attributed to the mineralocorticoid receptor (MR) signaling. Even though the rapid effects displayed by aldosterone are long known, our knowledge regarding the receptor responsible for such event is still poor. It is intense that the debate whether the MR or another receptor-the "unknown receptor"-is the receptor responsible for the rapid effects of aldosterone. Recently, G protein-coupled estrogen receptor-1 (GPER-1) was elegantly shown to mediate some aldosterone-induced rapid effects in several tissues, a fact that strongly places GPER-1 as the unknown receptor. It has also been suggested that angiotensin receptor type 1 (AT1) also participates in the aldosterone-induced rapid effects. Despite this open question, the relevance of the beneficial effects of aldosterone is clear in the kidneys, colon, and CNS as aldosterone controls the important water reabsorption process; on the other hand, detrimental effects displayed by aldosterone have been reported in the cardiovascular system and in the kidneys. In this line, the MR antagonists are well-known drugs that display beneficial effects in patients with heart failure and hypertension; it has been proposed that MR antagonists could also play an important role in vascular disease, obesity, obesity-related hypertension, and metabolic syndrome. Taken altogether, our goal here was to (1) bring a historical perspective of both genomic and rapid effects of aldosterone in several tissues, and the receptors and signaling pathways involved in such processes; and (2) critically address the controversial points within the literature as regarding which receptor participates in the rapid pathway display by aldosterone.

: Since the discovery of ischemic pre- and post-conditioning, more than 30 years ago, the knowledge about the mechanisms and signaling pathways involved in these processes has significantly increased. In clinical practice, on the other hand, such advancement has yet to be seen. This article provides an overview of ischemic pre-, post-, remote, and pharmacological conditioning related to the heart. In addition, we reviewed the cardioprotective signaling pathways and therapeutic agents involved in the above-mentioned processes, aiming to provide a comprehensive evaluation of the advancements in the field. The advancements made over the last decades cannot be ignored and with the exponential growth in techniques and applications. The future of pre- and post-conditioning is promising.

Mineralocorticoid receptor (MR) antagonists of aldosterone (spironolactone and eplerenone) display beneficial effects in the treatment of cardiopathies; however, many of these responses are independent of this antagonism. The mechanisms of action of these drugs are not well known; few studies have comparatively evaluated whether eplerenone as well as spironolactone display cardioprotective effects independent of the blockade of aldosterone. To study these mechanisms, which lead to cardioprotective responses, and to evaluate comparatively their effects in vitro, we have evaluated the proliferative effect of spironolactone and eplerenone in primary culture of cardiomyocytes and fibroblasts of neonatal Wistar rats in the presence and absence of aldosterone. Spironolactone and eplerenone promoted proliferation of cardiomyocyte even in the absence of aldosterone, suggesting a signaling pathway independent of the antagonism over aldosterone. Spironolactone was able to reduce the proliferation of fibroblasts and to reverse the proliferation promoted by aldosterone, which was also displayed by eplerenone. To elucidate the biochemical pathways evoked by these drugs, we sought to analyze Ca(2+), cAMP, and cGMP, and the activity of PKC and ERK1/2. Spironolactone and eplerenone increased the levels of Ca(2+), cGMP and activity of ERK 1/2, and reversed the action of aldosterone on the activity of PKC and ERK1/2. Interestingly, only spironolactone increased the levels of cAMP. Our data support the fact that in addition to aldosterone, both spironolactone and eplerenone display rapid responses (non-genomic) such as an increase on cAMP, Ca(2+), and cGMP by spironolactone, and Ca(2+) and cGMP by eplerenone. We have observed a more consistent cardioprotection promoted by spironolactone; however, these effects have yet to be tested clinically. Therefore, our data show that these drugs do not only act as an antagonist of MR, but could lead to a new pharmacological classification of these drugs.

Interaction among species, like ants and plants through extrafloral nectaries (EFNs), are important components of ecological communities' evolution. However, the effect of human disturbance on such specific interactions and its ecological consequences is poorly understood. This study evaluated the outcomes of mutualism between ants and the EFN-bearing plant Stachytarpheta glabra under anthropogenic disturbance. We compared the arthropod fauna composition between two groups of twenty plant individuals, one in an area disturbed by human activities and one in a preserved area. We also check the plant investment in herbivory defense and the consequential leaf damage by herbivore. Our results indicate that such disturbances cause simplification of the associated fauna and lack of proper ant mutualist. This led to four times more herbivory on plants of disturbed areas, despite the equal amount of EFN and ant visitors and low abundance of herbivores. The high pressure of herbivory may difficult the re-establishment of S. glabra, an important pioneer species in ferruginous fields, therefore it may affect resilience of this fragile ecological community.Keywords: arthropods, environmental conservation, Myrmecophily, rupestrian fields, Stachytarpheta glabra. Evidências de que os impactos antrópicos simplificam a fauna de formigaassociada a Stachytarpheta glabra (Verbenaceae) comprometendo os benefícios do mutualismo formiga-planta ResumoAs interações entre espécies, como por exemplo formigas e plantas através de nectários extraflorais (NEFs), são importantes componentes na evolução das comunidades. Entretanto, pouco é conhecido sobre os efeitos dos impactos antrópicos em interações específicas e suas consequências ecológicas. Este estudo avaliou os resultados do mutualismo entre formigas e NEF em Stachytarpheta glabra em área impactada pela atividade humana. Nós comparamos a composição e estrutura da fauna de artrópodes, em quarenta plantas de dois grupos, um impactado por atividades humanas e o outro preservado. Nós também avaliamos o investimento da planta em defesas contra herbívoros e os danos foliares causados por herbívoros. Nossos resultados indicam que os distúrbios causam a simplificação da faunaBraz.

Aldosterone acts on its target tissue through a classical mechanism or through the rapid pathway through a putative membrane-bound receptor. Our goal here was to better understand the molecular and biochemical rapid mechanisms responsible for aldosterone-induced cardiomyocyte hypertrophy. We have evaluated the hypertrophic process through the levels of ANP, which was confirmed by the analysis of the superficial area of cardiomyocytes. Aldosterone increased the levels of ANP and the cellular area of the cardiomyocytes; spironolactone reduced the aldosterone-increased ANP level and cellular area of cardiomyocytes. Aldosterone or spironolactone alone did not increase the level of cyclic 3',5'-adenosine monophosphate (cAMP), but aldosterone plus spironolactone led to increased cAMP level; the treatment with aldosterone + spironolactone + BAPTA-AM reduced the levels of cAMP. These data suggest that aldosterone-induced cAMP increase is independent of mineralocorticoid receptor (MR) and dependent on Ca(2+). Next, we have evaluated the role of A-kinase anchor proteins (AKAP) in the aldosterone-induced hypertrophic response. We have found that St-Ht31 (AKAP inhibitor) reduced the increased level of ANP which was induced by aldosterone; in addition, we have found an increase on protein kinase C (PKC) and extracellular signal-regulated kinase 5 (ERK5) activity when cells were treated with aldosterone alone, spironolactone alone and with a combination of both. Our data suggest that PKC could be responsible for ERK5 aldosterone-induced phosphorylation. Our study suggests that the aldosterone through its rapid effects promotes a hypertrophic response in cardiomyocytes that is controlled by an AKAP, being dependent on ERK5 and PKC, but not on cAMP/cAMP-dependent protein kinase signaling pathways. Lastly, we provide evidence that the targeting of AKAPs could be relevant in patients with aldosterone-induced cardiac hypertrophy and heart failure.