Bergantin Leandro Bueno
Department of Pharmacology-Universidade Federal de Sao Paulo-Escola Paulista de Medicina, Laboratory of Autonomic and Cardiovascular Pharmacology-55 11 5576-4973, Rua Pedro de Toledo, 669-Vila Clementino, Sao Paulo-SP, CEP: 04039-032, Brazil.
Curr Hypertens Rev. 2019;15(1):32-39. doi: 10.2174/1573402114666180817113242.
Hypertension, diabetes and neurodegenerative diseases are among the most prevalent medical problems around the world, costing millions of dollars to the medical health systems. Indeed, hypertension has been associated with higher risk for decline of cognition, as evidenced in patients with Alzheimer´s disease (AD). Furthermore, there is a clear relationship between hypertension and diabetes, reflecting substantial overlap in their etiology. Calcium (Ca2+) channel blockers (CCBs) have been classically prescribed for treating hypertension because of their mechanism of action due to reducing the influx of Ca2+ into the smooth muscles cells. In addition, many clinical and experimental studies have been demonstrating pleiotropic effects for CCBs. For instance, in hypertensive patients treated with CCBs, it can be observed lower incidence of neurodegenerative diseases such as AD. The virtual mechanism of action could be attributed to a restoration and maintenance of Ca2+ homeostasis, which is dysregulated in the neurodegenerative diseases, including also a reduction of neuronal apoptosis as part of these CCBs pleiotropic effects. Similarly, in hypertensive patients treated with CCBs, it can be observed an improvement of diabetes status such as glycemic control. A possible mechanism of action under debate could be attributed to a restoration of insulin secretion, then achieving glycemic control, and reduction of pancreatic β-cell apoptosis.
Considering the discovery of our group entitled "calcium paradox" due to Ca2+/cAMP signalling interaction, in this review I discussed the virtual involvement of this interaction in the pleiotropic effects of CCBs, including the possible role of the Ca2+/cAMP signalling interaction in the association between hypertension and higher risk for the decline of cognition, and diabetes.
高血压、糖尿病和神经退行性疾病是全球最普遍的医学问题，给医疗卫生系统造成数百万美元的成本。事实上，高血压与认知能力下降的风险较高有关，这在阿尔茨海默病（AD）患者中得到了证实。此外，高血压与糖尿病之间存在明显的关系，反映出它们在病因上有很大的重叠。钙（Ca2+）通道阻滞剂（CCBs）由于其作用机制是减少Ca2+流入平滑肌细胞，一直被经典地用于治疗高血压。此外，许多临床和实验研究已经证明CCBs具有多效性。例如，在用CCBs治疗的高血压患者中，可以观察到神经退行性疾病如AD的发病率较低。其实际作用机制可能归因于Ca2+稳态的恢复和维持，而Ca2+稳态在神经退行性疾病中失调，这也是这些CCBs多效性作用的一部分，包括神经元凋亡的减少。同样，在用CCBs治疗的高血压患者中，可以观察到糖尿病状况如血糖控制的改善。一个正在讨论的可能作用机制可能归因于胰岛素分泌的恢复，从而实现血糖控制，并减少胰腺β细胞凋亡。
考虑到我们小组因Ca2+/cAMP信号相互作用而发现的“钙悖论”，在这篇综述中，我讨论了这种相互作用在CCBs多效性作用中的实际参与情况，包括Ca2+/cAMP信号相互作用在高血压与认知能力下降和糖尿病风险增加之间关联中的可能作用。
