Hypertension
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Comparative Study
The impact of microsomal prostaglandin e synthase 1 on blood pressure is determined by genetic background.
Prostaglandin (PG)E(2) has multiple actions that may affect blood pressure. It is synthesized from arachidonic acid by the sequential actions of phospholipases, cyclooxygenases, and PGE synthases. Although microsomal PGE synthase (mPGES)1 is the only genetically verified PGE synthase, results of previous studies examining the consequences of mPGES1 deficiency on blood pressure (BP) are conflicting. ⋯ Urinary excretion of thromboxane was unaffected by angiotensin II in the DBA/1 lines but increased more than 4-fold in 129 mPGES1(-/-) mice. These data indicate that genetic background significantly modifies the BP response to mPGES1 deficiency. Exaggerated production of thromboxane may contribute to the robust hypertension and albuminuria in 129 mPGES1-deficient mice.
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Multicenter Study Comparative Study
Baseline depressive symptoms are not associated with clinically important levels of incident hypertension during two years of follow-up: the multi-ethnic study of atherosclerosis.
Previous longitudinal cohort studies have suggested an association between baseline depressive symptoms and incident hypertension. We assessed this possible association using data from the Multi-ethnic Study of Atherosclerosis, a population-based prospective cohort study of 6814 US adults from 4 different racial/ethnic groups. Baseline users of antihypertensive medications and participants lost to follow-up were excluded leaving 3914 participants. ⋯ Using relative risk regression, patients with baseline depressive symptoms did not have an increased risk of incident hypertension (relative risk: 1.02; 95% confidence interval [CI]: 0.99 to 1.05), although an association between tricyclic antidepressants and hypertension (relative risk: 1.20; 95% CI: 1.05 to 1.37) was observed in subgroup analysis. Depression, even after adjustment for covariates, was associated with small changes in systolic (+2.4 mm Hg; 95% CI: 0.2 to 4.7) and diastolic (+0.8 mm Hg; 95% CI: -0.6 to 2.3) blood pressures. Depressive symptoms may be associated with slight increases in blood pressure in this multiethnic cohort, but it is premature to conclude much without longer studies in other populations.
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Comparative Study
mPGES-1 protects against DOCA-salt hypertension via inhibition of oxidative stress or stimulation of NO/cGMP.
Microsomal prostaglandin E synthase-1 (mPGES-1) is a recently characterized cytokine-inducible enzyme critically involved in pain and inflammatory response. However, its role in blood pressure regulation is still debatable. The present study was undertaken to examine the effect of mPGES-1 deletion on DOCA-salt hypertension. ⋯ Immunoblotting demonstrated increased renal expression of mPGES-1 in DOCA-salt WT mice. DOCA-salt induced a nearly 5-fold increase in urinary PGE(2) excretion in the WT mice, and this increase was completely abolished in the KO mice. Together, these results suggest that mPGES-1-derived PGE(2) confers protection against DOCA-salt hypertension likely via inhibition of oxidative stress or stimulation of superoxide dismutase-3 and urinary nitrate/nitrite system.
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Mechanisms of formation and growth of intracranial aneurysms are poorly understood. To investigate the pathophysiology of intracranial aneurysms, an animal model of intracranial aneurysm yielding a high incidence of large aneurysm formation within a short incubation period is needed. We combined two well-known clinical factors associated with human intracranial aneurysms, hypertension and the degeneration of elastic lamina, to induce intracranial aneurysm formation in mice. ⋯ MMP-9 knockout mice, but not MMP-2 knockout mice, had reduced the incidence of intracranial aneurysms. In summary, a stereotaxic injection of elastase into the basal cistern in hypertensive mice resulted in intracranial aneurysms that closely resembled human intracranial aneurysms. The intracranial aneurysm formation in this model appeared to depend on MMP activation.
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Recent studies suggest that vascular risk factors play a considerable role in the development of Alzheimer disease. Furthermore, the use of antihypertensive drugs has been suggested to reduce the incidence of dementia, including Alzheimer disease. In this study, we examined the effects of an angiotensin receptor blocker, olmesartan, on beta-amyloid-induced cerebrovascular dysfunction and cognitive impairment. ⋯ Olmesartan significantly improved cognitive function independent of its blood pressure-lowering effect, whereas there was no improvement by other types of antihypertensive drugs (hydralazine and nifedipine). We found that pretreatment with a low dose of olmesartan completely prevented beta-amyloid-induced vascular dysregulation and partially attenuated the impairment of hippocampal synaptic plasticity. These findings suggest the possibility that amelioration of cerebrovascular dysfunction with an angiotensin receptor blocker could be a novel therapeutic strategy for the early stage of Alzheimer disease.