RESUMO
Diabetes mellitus and hypertension are diseases that are strongly correlated. A major factor in this correlation is the renin-angiotensin system (RAS), with the peptide angiotensin II being a key component. This study analyzed the impact of Angiotensin Type 1 receptor (AT1R) and Angiotension Type 2 receptor (AT2R) in atrial function. MAIN METHODS: To perform the experiments, Wistar Kyoto rats (WKY), diabetic streptozotocin-induced WKY rats and spontaneously hypertensive rats (SHR) were used, and stimulation of cardiovascular function was done by means of the following drugs: angiotensin II, novokinin and the antagonists losartan and PD123177. We also measured the systolic blood pressure (SBP). RESULTS: An increase in AT1R function was observed in diabetic and hypertensive rats (18% in right atria [RA] and 11% in left atria [LA]). We also observed an increase in calcium release from the endoplasmic reticulum in right atria of diabetic rats (31%) and in right atria of hypertensive rats (35%). On the other hand, a decreased response of AT2R in diabetic and hypertensive rats was observed, this decreased response was greater in hypertensive rats (RA, 10%; LA, 12%). These results have demonstrated a dysfunction of the RAS that may contribute to the common dysfunctions of the cardiovascular system in diabetic and hypertensive rats.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Átrios do Coração/fisiopatologia , Contração Muscular , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Animais , Pressão Sanguínea , Diabetes Mellitus Experimental/metabolismo , Ratos , Ratos Endogâmicos SHRRESUMO
It is known that chronic ethanol (EtOH) consumption leads to hypertension development and has been associated with deleterious effects on the cardiovascular system. Whether this condition alters calcium (Ca2+) signaling and exocytosis in adrenal chromaffin cells (CCs) as the case is for genetic hypertension, is unknown. We explored this question in four randomized experimental groups, male Wistar Kyoto (WKY/EtOH) and Spontaneously Hypertensive (SHR/EtOH) rats were subjected to the intake of increasing EtOH concentrations (5-20%, for 30 days) and their respective controls (WKY/Control and SHR/Control) received water. WKY/EtOH developed hypertension and cardiac hypertrophy; blood aldehyde dehydrogenase (ALDH) and H2O2 were also augmented. In comparison with WKY/Control, CCs from WKY/EtOH had the following features: (i) depolarization and higher frequency of spontaneous action potentials; (ii) decreased Ca2+ currents with slower inactivation; (iii) decreased K+ currents; (iv) augmented K+-elicited cytosolic Ca2+ transients ([Ca2+]c); (v) enhanced K+-elicited catecholamine release. These cardiovascular, blood and CCs changes were qualitatively similar to those undergone by SHR/Control and SHR/EtOH. The results suggest that the hypertension elicited by chronic EtOH has pathogenic features common to genetic hypertension namely, augmented [Ca2+]c transients and catecholamine release from their CCs.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Catecolaminas/metabolismo , Células Cromafins/efeitos dos fármacos , Células Cromafins/metabolismo , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Hipertensão/induzido quimicamente , Hipertensão/patologia , Potenciais de Ação/efeitos dos fármacos , Animais , Cálcio/metabolismo , Células Cromafins/patologia , Citosol/efeitos dos fármacos , Citosol/metabolismo , Etanol/farmacologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Potássio/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fatores de TempoRESUMO
BACKGROUND: Chronic ethanol (EtOH) consumption has been associated with deleterious effects on the cardiovascular system by abnormal calcium (Ca2+) handling. Store-operated Ca2+ entry (SOCE) is related to cardiovascular remodeling which leads to the hypertension development, and the coupling between STIM-1 (ER Ca2+ sensor) and Orai-1 (channel pore) is a key mechanism to control SOCE through of store-operated Ca2+ channels (SOCCs). However, the role of STIM-1/Orai-1-mediated SOCE and its cross-talk with EtOH-triggered vascular remodeling and hypertension remain poorly understood. We address this subject in the present study by evaluating how chronic EtOH consumption induces alterations in Ca2+ handling via SOCE. METHODS: Male Wistar Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats were subjected to the intake of increasing EtOH concentrations (5-20%, for 30 days). Systolic blood pressure (SBP) and EtOH concentration were measured; cardiovascular remodeling was assessed by histomorphometry; and function/ expression of STIM-1/Orai-1-mediated Ca2+ influx were evaluated by isometric contraction and western blot experiments. RESULTS: Compared to the WKY-Control, our results show that: (1) chronic EtOH consumption caused a significant elevation of SBP in both strains; (2) cardiac hypertrophy and hypertrophic aortic wall remodeling much more pronounced in WKY-EtOH; (3) decreased capacity of ER to store and release Ca2+; (4) increased STIM-1/Orai-1-mediated SOCCs activation, which was selectively inhibited by YM-58483; and (5) increased expression of STIM-1 in WKY-EtOH and SHR-Control rats. CONCLUSION: These findings suggest that hypertrophic aortic remodeling and abnormal contraction triggered mainly by Ca2+ overload via STIM-1/Orai-1-mediated SOCE through SOCCs are involved hypertension developed by EtOH consumption.