Hypertension, Diabetes and Neurodegenerative Diseases: Is there a Clinical Link through the Ca2+/cAMP Signalling Interaction?

Author(s): Leandro Bueno Bergantin*.

Journal Name: Current Hypertension Reviews

Volume 15 , Issue 1 , 2019

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Abstract:

Background: 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.

Conclusion: 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.

Keywords: Hypertension, diabetes, neurodegenerative diseases, Ca2+/cAMP signalling interaction, Alzheimer's disease, apoptosis.

[1]
Marfany A, Sierra C, Camafort M, Doménech M, Coca A. High blood pressure, Alzheimer disease and antihypertensive treatment. Panminerva Med 2018; 60(1): 8-16.
[2]
Bergantin LB, Caricati-Neto A. Challenges for the pharmacological treatment of neurological and psychiatric disorders: Implications of the Ca2+/cAMP intracellular signalling interaction. Eur J Pharmacol 2016; 788: 255-60.
[3]
Bergantin LB, Souza CF, Ferreira RM, et al. Novel model for “calcium paradox” in sympathetic transmission of smooth muscles: role of cyclic AMP pathway. Cell Calcium 2013; 54(3): 202-12.
[4]
Caricati-Neto A, Garcia AG, Bergantin LB. Pharmacological implications of the Ca2+/cAMP signaling interaction: From risk for antihypertensive therapy to potential beneficial for neurological and psychiatric disorders. Pharmacol Res Perspect 2015; 3(5): e00181.
[5]
Mattson MP, Bezprozvanny I. Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends Neurosci 2008; 31(9): 454-63.
[6]
Wu CL, Wen SH. A 10-year follow-up study of the association between calcium channel blocker use and the risk of dementia in elderly hypertensive patients. Medicine (Baltimore) 2016; 95(32): e4593.
[7]
Yulia K, Anath S, Stuart JF, April PC, Monika MS. Calcium channel blocker use is associated with lower fasting serum glucose among adults with diabetes from the REGARDS study. Diabetes Res Clin Pract 2016; 115: 115-21.
[8]
Bernard MYC, Chao L. Diabetes and hypertension: Is there a common metabolic pathway? Curr Atheroscler Rep 2012; 14(2): 160-6.
[9]
Weycker D, Nichols GA, O’Keeffe-Rosetti M, et al. Excess risk of diabetes in persons with hypertension. Diabetes Complications 2009; 23(5): 330-6.
[10]
Xu G, Chen J, Jing G, Shalev A. Preventing beta-cell loss and diabetes with calcium channel blockers. Diabetes 2012; 61(4): 848-56.
[11]
Iadecola C, Yaffe K, Biller J, et al. Impact of hypertension on cognitive function. A scientific statement from the American Heart Association. Hypertension 2016; 68: e67-94.
[12]
Qiu C, Winblad B, Fratiglioni L. The age dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 2005; 4: 487-99.
[13]
Kennelly S, Collins O. Walking the cognitive “minefield” between high and low blood pressure. J Alzheimers Dis 2012; 32: 609-21.
[14]
Ashby EL, Miners JS, Kehoe PG, Love S. Effects of hypertension and anti-hypertensive treatment on amyloid-ß plaque load and Aß- synthesizing and Aß-degrading enzymes in frontal cortex. J Alzheimers Dis 2016; 50: 1191-203.
[15]
Walker KA, Power MC, Gottesman RF. Defining the relationship between hypertension, cognitive decline, and dementia: A review. Curr Hypertens Rep 2017; 19: 24.
[16]
Langbaum JBS, Chen K, Launer LJ, et al. Blood pressure is associated with higher brain amyloid burden and lower glucose metabolism in healthy late middle-age persons. Neurobiol Aging 2012; 33: 827.e11-9.
[17]
Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42: 2672-713.
[18]
Caricati-Neto A, Bergantin LB. Pharmacological modulation of neural Ca2+/camp signaling interaction as therapeutic goal for treatment of Alzheimer’s disease. J Syst Integr Neurosci 2017; 3
[http://dx.doi.org/10.15761/JSIN.1000185]
[19]
Caricati-Neto A, Bergantin LB. The passion of a scientific discovery: the “calcium paradox” due to Ca2+/camp interaction. J Syst Integr Neurosci 2017; 3
[http://dx.doi.org/10.15761/JSIN.1000186]
[20]
Caricati-Neto A, Bergantin LB. 2017 From a “eureka insight” to a novel potential therapeutic target to treat Parkinson’s disease: The Ca2+/camp signalling interaction. J Syst Integr Neurosci4
[http://dx.doi.org/10.15761/JSIN.1000187]
[21]
Rouch L, Cestac P, Hanon O, et al. Antihypertensive drugs, prevention of cognitive decline and dementia: A systematic review of observational studies, randomized controlled trials and meta-analyses, with discussion of potential mechanisms. CNS Drugs 2015; 29: 113-30.
[22]
Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur). Trial Investigators Lancet 1997; 350: 757-64.
[23]
Forette F, Seux ML, Staessen JA, et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 1998; 352: 1347-51.
[24]
Di Bari M, Pahor M, Franse LV, et al. Dementia and disability outcomes in large hypertension trials: Lessons learned from the systolic hypertension in the elderly program (SHEP) trial. Am J Epidemiol 2001; 153: 72-8.
[25]
Cheung BM. The hypertension-diabetes continuum. J Cardiovasc Pharmacol 2010; 55: 333-9.
[26]
Landsberg L, Molitch M. Diabetes and hypertension: Pathogenesis, prevention and treatment. Clin Exp Hypertens 2004; 26: 621-8.
[27]
Gress TW, Nieto FJ, Shahar E, et al. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis risk in communities study. N Engl J Med 2000; 342: 905-12.
[28]
Cheung BM, Wat NM, Tso AW, et al. Association between raised blood pressure and dysglycemia in Hong Kong Chinese. Diabetes Care 2008; 31: 1889-91.
[29]
Penner R, Neher E. The role of calcium in stimulus-secretion coupling in excitable and non-excitable cells. J Exp Biol 1988; 139: 329-45.
[30]
Miranda-Ferreira R, de Pascual R, de Diego AM, et al. Single-vesicle catecholamine release has greater quantal content and faster kinetics in chromaffin cells from hypertensive, as compared with normotensive, rats. J Pharmacol Exp Ther 2008; 324(2): 685-93.
[31]
Miranda-Ferreira R, de Pascual R, Caricati-Neto A, Gandia L, Jurkiewicz A, Garcia AG. Role of the endoplasmic reticulum and mitochondria on quantal catecholamine release from chromaffin cells of control and hypertensive rats. J Pharmacol Exp Ther 2009; 329(1): 231-40.
[32]
Miranda-Ferreira R, de Pascual R, Smaili SS, et al. Greater cytosolic and mitochondrial calcium transients in adrenal medullary slices of hypertensive, compared with normotensive rats. Eur J Pharmacol 2010; 636(1-3): 126-36.
[33]
Draznin B. Intracellular calcium, insulin secretion, and action. Am J Med 1988; 85(5A): 44-58.
[34]
Ahn C, Kang J-HChanghwan Ahn, Ji-Houn Kang, Eui-Bae, Jeung E-B. Calcium homeostasis in diabetes mellitus. J Vet Sci 2017; 18(3): 261-6.
[35]
Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993; 361(6407): 31-9.
[36]
Larkman AU, Jack JJ. Synaptic plasticity: Hippocampal LTP. Curr Opin Neurobiol 1995; 5(3): 324-34.
[37]
Nicoll RA, Malenka RC. Contrasting properties of two forms of long-term potentiation in the hippocampus. Nature 1995; 377(6545): 115-8.
[38]
Bratanova-Tochkova TK, Cheng H, Daniel S, et al. Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion. Diabetes 2002; 51(Suppl. 1): S83-90.
[39]
Hedeskov CJ. Mechanism of glucose-induced insulin secretion. Physiol Rev 1980; 60(2): 442-509.
[40]
Henquin JC. The interplay between cyclic AMP and ions in the stimulus-secretion coupling in pancreatic B-cells. Arch Int Physiol Biochim 1985; 93(1): 37-48.
[41]
Sharp GW. The adenylate cyclase-cyclic AMP system in islets of Langerhans and its role in the control of insulin release. Diabetologia 1979; 16(5): 287-96.
[42]
Sutherland EW, Robison GA. The role of cyclic AMP in the control of carbohydrate metabolism. Diabetes 1969; 18(12): 797-819.
[43]
Fujita-Yoshigaki J. Divergence and convergence in regulated exocytosis: the characteristics of cAMP-dependent enzyme secretion of parotid salivary acinar cells. Cell Signal 1998; 10(6): 371-5.
[44]
Bergantin LB, Caricati-Neto A. Insight from “Calcium Paradox” due to Ca2+/cAMP interaction: Novel pharmacological strategies for the treatment of depression. Int Arch Clin Pharmacol 2016; 2: 007.
[45]
Bergantin LB, Caricati-Neto A. Novel concepts for clinical pharmacology from "Calcium Paradox" due to neuronal interaction between signalling pathways mediated by Ca2+ and cAMP: From 1975 to 2017. Int Arch Clin Pharmacol 2017; 3: 013.
[46]
Bergantin LB. Neurodegenerative diseases: Where to go from now? thought provoking through Ca2+/cAMP signaling interaction. Brain Disord Ther 2017; 6: e125.
[47]
Bergantin LB. Neurological Disorders: Is There a Horizon? Emerging Ideas from the Interaction between Ca2+ and Camp Signaling Pathways. J Neurol Disord 2017; 5: e124.
[48]
Giovannucci DR, Groblewski GE, Sneyd J, Yule DI. Targeted phosphorylation of inositol 1,4,5-trisphosphate receptors selectively inhibits localized Ca2+ release and shapes oscillatory Ca2+ signals. J Biol Chem 2000; 275(43): 33704-11.
[49]
Bruce JI, Shuttleworth TJ, Giovannucci DR, Yule DI. Phosphorylation of inositol 1,4,5-trisphosphate receptors in parotid acinar cells. A mechanism for the synergistic effects of cAMP on Ca2+ signaling. J Biol Chem 2002; 277(2): 1340-8.
[50]
Chatton JY, Cao Y, Liu H, Stucki JW. Permissive role of cAMP in the oscillatory Ca2+ response to inositol 1,4,5-trisphosphate in rat hepatocytes. Biochem J 1998; 330(Pt 3): 1411-6.
[51]
Lee RJ, Foskett JK. cAMP-activated Ca2+ signaling is required for CFTR-mediated serous cell fluid secretion in porcine and human airways. J Clin Invest 2010; 120(9): 3137-48.
[52]
Douglas WW, Rubin RP. The role of calcium in the secretory response of the adrenal medulla to acetylcholine. J Physiol 1961; 159: 40-57.
[53]
Baker PF, Knight DE. Calcium-dependent exocytosis in bovine adrenal medullary cells with leaky plasma membranes. Nature 1978; 276(5688): 620-2.
[54]
Kreye VA, Luth JB. Proceedings: Verapamil-induced phasic contractions of the isolated rat vas deferens. Naunyn Schmiedebergs Arch Pharmacol 1975; 287(Suppl.): R43.
[55]
French AM, Scott NC. A comparison of the effects of nifedipine and verapamil on rat vas deferens. Br J Pharmacol 1981; 73(2): 321-3.
[56]
Moritoki H, Iwamoto T, Kanaya J, Maeshiba Y, Ishida Y, Fukuda H. Verapamil enhances the non-adrenergic twitch response of rat vas deferens. Eur J Pharmacol 1987; 140(1): 75-83.
[57]
Bergantin LB, Caricati-Neto A. Emerging concepts for neuroscience field from Ca2+/cAMP signalling interaction. J Neurol Exp Neurosci 2017; 3(1): 29-32.
[58]
Bergantin LB. Advances for the pharmacotherapy of depression - Presenting the rising star: Ca2+/camp signaling interaction. J Syst Integr Neurosci 2017; 3
[http://dx.doi.org/10.15761/JSIN.1000161]
[59]
Bergsten P. Calcium dysregulation, insulin release and the pathogenesis of diabetesAdv Cell Aging Gerontol 2003.doi.org/101016/S1566-3124(02)10020-4
[60]
Sommer N, Loschmann PA, Northoff GH, et al. The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis. Nat Med 1995; 1: 244-8.
[61]
Xiao L, O’Callaghan JP, O’Donnell JM. Effects of repeated treatment with phosphodiesterase-4 inhibitors on cAMP signaling, hippocampal cell proliferation, and behavior in the forced-swim test. J Pharmacol Exp Ther 2011; 338: 641-7.


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VOLUME: 15
ISSUE: 1
Year: 2019
Page: [32 - 39]
Pages: 8
DOI: 10.2174/1573402114666180817113242
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