Abstract-Rat models of hypertension, eg, spontaneously hypertensive stroke-prone rats (SHRSP), display reduced angiotensin-converting enzyme 2 (ACE2) mRNA and protein expression compared with control animals. The aim of this study was to investigate the role of ACE2 in the pathogenesis of hypertension in these models. Therefore, we generated transgenic rats on a SHRSP genetic background expressing the human ACE2 in vascular smooth muscle cells by the use of the SM22 promoter, called SHRSP-ACE2. In these transgenic rats vascular smooth muscle expression of human ACE2 was confirmed by RNase protection, real-time RT-PCR, and ACE2 activity assays. Transgene expression leads to significantly increased circulating levels of angiotensin-(1-7), a prominent product of ACE2. Mean arterial blood pressure was reduced in SHRSP-ACE2 compared to SHRSP rats, and the vasoconstrictive response to intraarterial administration of angiotensin II was attenuated. The latter effect was abolished by previous administration of an ACE2 inhibitor. To evaluate the endothelial function in vivo, endothelium-dependent and endothelium-independent agents such as acetylcholine and sodium nitroprusside, respectively, were applied to the descending thoracic aorta and blood pressure was monitored. Endothelial function turned out to be significantly improved in SHRSP-ACE2 rats compared to SHRSP. These data demonstrate that vascular ACE2 overexpression in SHRSP reduces hypertension probably by locally degrading angiotensin II and improving endothelial function. Thus, activation of the ACE2/angiotensin-(1-7) axis may be a novel therapeutic strategy in hypertension. (Hypertension. 2008;52:967-973.)
Accumulating evidence indicates that various biological and neuroendocrine circadian rhythms may be disrupted in cardiovascular and metabolic disorders. These circadian alterations may contribute to the progression of disease. Our studies direct to an important role of angiotensin II and melatonin in the modulation of circadian rhythms. The brain renin-angiotensin system (RAS) may modulate melatonin synthesis, a hormone with well-established roles in regulating circadian rhythms. Angiotensin production in the central nervous system may not only influence hypertension but also appears to affect the circadian rhythm of blood pressure. Drugs acting on RAS have been proven effective in the treatment of cardiovascular and metabolic disorders including hypertension and diabetes mellitus (DM). On the other hand, since melatonin is capable of ameliorating metabolic abnormalities in DM and insulin resistance, the beneficial effects of RAS blockade could be improved through combined RAS blocker and melatonin therapy. Contemporary research is evidencing the existence of specific clock genes forming central and peripheral clocks governing circadian rhythms. Further research on the interaction between these two neurohormones and the clock genes governing circadian clocks may progress our understanding on the pathophysiology of disease with possible impact on chronotherapeutic strategies.
Background: The COVID-19 pandemic continues to rise. In order to control the COVID-19 pandemic, healthcare professionals have been subjected to increased exposure to work stress. In this systematic review, we aimed at investigating the prevalence and determinants of immediate and long-term post-traumatic stress disorder (PTSD) effects on healthcare professionals by the COVID-19 (SARS CoV-2) and SARS-2003 (SARS CoV-1) pandemics. Methods: This systematic review was conducted according to the recommendations of the Protocols for Systemic Review and Meta-Analysis (PRISMA) statement. Only studies reporting the prevalence of PTSD (frequency, percentage) and related risk factors (adjusted odds ratio (OR)) in healthcare professionals (HCPs) during the SARS CoV-2 and SARS CoV-1 pandemics were included. The following databases were screened: Medline, Embase, PsychINFO, and Health Psychosocial Instrument (HaPI). Results: Six of eight studies reported PTSD symptoms among healthcare professionals during the COVID-19 pandemic in China (three), Singapore (one), India (one), and the United States of America (USA) (two), while two studies reported symptoms during the SARS-2003 pandemic in China (one) and Singapore (one). Sample sizes ranged from 263 to 5062 with a combined total of 10,074 participants. All of the studies self-reported the level of exposure to coronaviruses (CoV-1 and CoV-2) and severity of PTSD. Seven studies reported the prevalence of immediate PTSD and determinants, while one study reported delayed-onset PTSD (3 years after CoV-1 pandemic). Determinants of immediate PTSD were reported for the CoV-2 pandemic, while those for long-term PTSD were reported for the CoV-1 pandemic. Conclusions: A comprehensive understanding of the prevalence and determinants of immediate or long-term pandemic PTSD for healthcare workers can improve prevention, diagnosis, and management. Rigorous research measuring the prevalence of PTSD and its associated risk factors (adjusted OR) for the CoV-2 pandemic are envisaged. Although strategies to resolve immediate PTSD are key, long-term PTSD must not be overlooked.
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