Background:
β-blockers are no longer considered as first-line antihypertensive drugs due to their lower cardioprotection.
Method:
Considering the differences in the pharmacological properties of β-blockers, the present work compared the effects of third-generation β-blockers – carvedilol and nebivolol – with a first-line agent – amlodipine – on hemodynamic parameters, including short-term blood pressure variability (BPV), and their ability to prevent target organ damage in spontaneously hypertensive rats (SHR). SHR rats were orally treated with carvedilol, nebivolol, atenolol, amlodipine or vehicle for 8 weeks. Wistar Kyoto rats treated with vehicle were used as normotensive group. Echocardiographic evaluation, BP, and short-term BPV measurements were performed. Left ventricle and thoracic aorta were removed for histological evaluations and to assess the expression of transforming growth factor β (TGF-β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).
Results:
Carvedilol, nebivolol or amlodipine induced a greater reduction of carotid BP, short-term BPV and echocardiography parameters than atenolol in SHR rats. Carvedilol, nebivolol and amlodipine were more effective than atenolol in the prevention of cardiac hypertrophy, and cardiac and aortic collagen deposit. Carvedilol and nebivolol, but not atenolol, reduced the expressions of fibrotic and inflammatory biomarkers – TGF-β, TNF-α and IL-6 – in SHR rats to a similar extent to that of amlodipine.
Conclusion:
Chronic treatment with carvedilol or nebivolol attenuates carotid BP and short-term BPV, and reduces target organ damage in SHR to a greater extent than atenolol. Our findings suggest that the lower cardiovascular protection of nonvasodilating β-blockers, as atenolol, in hypertension must not be translated to third-generation β-blockers.
Accumulation of calcium is proposed to account for selective dopaminergic neuron (DN) dysfunctionality, a characteristic of Parkinson´s Disease (PD). To test the in vivo impact of calcium increment in DN physiology we downregulated the Plasma Membrane Calcium ATPase (PMCA), a bomb that extrudes cytosolic calcium, in those neurons in Drosophila melanogaster. Using th-GAL4>PMCA RNAi , PMCA was selectively reduced, leading to increased cytosolic calcium and mitochondrial oxidative stress with no neurodegeneration. In the eye, PMCA RNAi expression provoked a subtle disorganization, suggesting scarce toxicity. Interestingly, we observed several locomotor alterations and a higher level of dopamine in brains. Finally, flies presented a reduction of lifespan and a perimortem nonmotor phenotype characterized by abdominal swelling, possibly due to constipation. We conclude that elevated cytosolic calcium in DN could trigger cellular dysfunction generating mitochondrial oxidative stress and motor and non-motor symptoms, typical of PD.
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