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These findings indicate that aldosterone/salt-induced renal injury and fibrosis has inflammatory components involving macrophage infiltration and cytokine up-regulation. Attenuation of renal damage and inflammation by eplerenone supports the protective effects of aldosterone blockade in hypertensive renal disease.

Vascular inflammation was examined as a potential mechanism of aldosterone-mediated myocardial injury in uninephrectomized rats receiving 1% NaCl-0.3% KCl to drink for 1, 2, or 4 wk and 1) vehicle, 2) aldosterone infusion (0.75 microg/h), or 3) aldosterone infusion (0.75 microg/h) plus the selective aldosterone blocker eplerenone (100 mg. kg(-1). day(-1)). Aldosterone induced severe hypertension at 4 wk [systolic blood pressure (SBP), 210 +/- 3 mmHg vs. vehicle, 131 +/- 2 mmHg, P < 0.001], which was partially attenuated by eplerenone (SBP, 180 +/- 7 mmHg; P < 0.001 vs. aldosterone alone and vehicle). No significant increases in myocardial interstitial collagen fraction or hydroxyproline concentration were detected throughout the study. However, histopathological analysis of the heart revealed severe coronary inflammatory lesions, which were characterized by monocyte/macrophage infiltration and resulted in focal ischemic and necrotic changes. The histological evidence of coronary lesions was preceded by and associated with the elevation of cyclooxygenase-2 (up to approximately 4-fold), macrophage chemoattractant protein-1 (up to approximately 4-fold), and osteopontin (up to approximately 13-fold) mRNA expression. Eplerenone attenuated proinflammatory molecule expression in the rat heart and subsequent vascular and myocardial damage. Thus aldosterone and salt treatment in uninephrectomized rats led to severe hypertension and the development of a vascular inflammatory phenotype in the heart, which may represent one mechanism by which aldosterone contributes to myocardial disease.

Abstract-Chronic treatment of saline-drmkmg stroke-prone spontaneously hypertensive rats (SHRSP) with agents that interfere with the formation or actions of angotensm II (Ang II) prevents the development of stroke and renal vascular damage Ang II, m addltlon to its direct vascular effects, stimulates the synthesis and release of aldosteroneTo assess the role of aldosterone m the development of pathologc changes m these rats, we implanted time-release pellets containing 200 mg of the mmeralocortlcold receptor antagomst, spu-onolactone, mto 14 SHRSP at 7 5 weeks of age Eight SHRSP httermates received placebo pellets Over the period of study (3 to 4 weeks), systolic blood pressure (SBP) (PRA) and aldosterone as independent nsk factors for heart attack and stroke ' They found that among the patients who developed strokes and myocardlal mfarctlons, all had normal or high PRA, and aldosterone secretlon Previous studies by our group and others have provided expenmental evidence to support a role for the renm-angotensm-aldosterone system (RAAS) m the development of vascular qury, as angotensm converting enzyme (ACE) mhlbltors2-6 and Ang II receptor antagonlsts7-9 prevented the development of stroke and malignant nephrosclerosls m SHRSP Since these studies were conducted m salt-loaded SHRSP, which respond to these agents with nummal blood pressure lowermg, they provided evidence for a pathophyslolog& role for Ang II m the development of vascular lesions of malignant nephrosclerosls independent of severely elevated blood pressure Consistent with a role for Ang II was the finding that SHRSP display a paradoxical increase m PRA with rime, despite continued salt-loading 3 9,'" Although Ang II stimulates the synthesis and release of aldosterone," " m addmon to its direct vascular actions, a role for mmeralocortlcolds m the pathology of SHRSP

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MotivationThe BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community‐led open‐source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.Main types of variables includedThe database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.Spatial location and grainBioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2).Time period and grainBioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.Major taxa and level of measurementBioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.Software format.csv and .SQL.

Abstract-Stroke-prone spontaneously hypertensive rats (SHRSP) on 1% NaCl drinking solution and Stroke-Prone Rodent Diet develop severe hypertension and glomerular and vascular lesions characteristic of thrombotic microangiopathy seen in malignant nephrosclerosis. We recently reported that spironolactone, a mineralocorticoid receptor antagonist, markedly reduced proteinuria and malignant nephrosclerotic lesions in these animals. This observation, together with our previous findings that angiotensin-converting enzyme inhibitors prevent the development of vascular damage, suggests that mineralocorticoids, as part of the renin-angiotensin-aldosterone system, play a pathophysiological role in this model. In the present study, we examined whether chronic (2-week) infusion of aldosterone can reverse the renal vascular protective effects of captopril in SHRSP. SHRSP received vehicle (nϭ8); captopril alone (50 mg ⅐ kg; or captopril and aldosterone at 20 (nϭ6) or. Systolic blood pressure was markedly elevated in all groups. Vehicle-and aldosterone-infused SHRSP developed severe proteinuria and comparable degrees of renal injury (21Ϯ3% and 29Ϯ3%, respectively) manifested as thrombotic and proliferative lesions in the arterioles and glomeruli. Captopril treatment reduced plasma aldosterone levels concomitant with marked reductions in proteinuria and the absence of histologic lesions of malignant nephrosclerosis. Aldosterone substitution at 20 or 40 g ⅐ kg Ϫ1 ⅐ d Ϫ1 in captopril-treated SHRSP resulted in the development of severe renal lesions (16Ϯ3% and 21Ϯ2%, respectively) and proteinuria comparable with that observed in SHRSP given either aldosterone or vehicle alone. These findings support a major role for aldosterone in the development of malignant nephrosclerosis in saline-drinking SHRSP, independent of the effects of blood pressure. Key Words: hypertension Ⅲ kidney Ⅲ malignant nephrosclerosis Ⅲ captopril Ⅲ aldosterone T he participation of the renin-angiotensin-aldosterone system (RAAS) in the development of hypertensive vascular injury has been widely demonstrated. 1 Numerous studies with angiotensin-converting enzyme (ACE) inhibitors and with angiotensin (Ang) II receptor antagonists have clearly identified Ang II as a major factor responsible for the development of end-organ damage in hypertensive vascular disease. However, mineralocorticoids may also play an important role, because animals with deoxycorticosterone acetate (DOCA)-salt hypertension typically develop severe vascular pathology, and resultant malignant nephrosclerosis, myocardial necrosis, and stroke, 2-5 despite low levels of plasma renin activity. 2,5,6 The renal lesions that develop in DOCA-salt hypertensive rats are characterized by fibrinoid necrosis of blood vessels and proliferative arteriopathy 2-4 and are very similar to those seen in stroke-prone spontaneously hypertensive rats (SHRSP) receiving a high sodium chloride diet 7-11 and in rats with Ang II-salt-induced hypertension. 12 We have shown that chronic administration of agents that inter...

We studied the role of aldosterone (aldo) in myocardial injury in a model of angiotensin (Ang) II-hypertension. Wistar rats were given 1% NaCl (salt) to drink and randomized into one of the following groups (n = 10; treatment, 21 d): 1) vehicle control (VEH); 2) Ang II infusion (25 ng/min, sc); 3) Ang II infusion plus the selective aldo blocker, eplerenone (epl, 100 mg/kg.d, orally); 4) Ang II infusion in adrenalectomized (ADX) rats; and 5) Ang II infusion in ADX rats with aldo treatment (20 micro g/kg.d, sc). ADX rats received also dexamethasone (12 micro g/kg.d, sc). Systolic blood pressure increased with time in all treatment groups except the VEH group (VEH, 136 +/- 6; Ang II/NaCl, 203 +/- 12; Ang II/NaCl/epl, 196 +/- 10; Ang II/NaCl/ADX, 181 +/- 7; Ang II/NaCl/ADX/aldo, 236 +/- 8 mm Hg). Despite similar levels of hypertension, epl and ADX attenuated the increase in heart weight/body weight induced by Ang II. Histological examination of the hearts evidenced myocardial and vascular injury in the Ang II/salt (7 of 10 hearts with damage, P < 0.05 vs. VEH) and Ang II/salt/ADX/aldo groups (10 of 10 hearts with damage, P < 0.05). Injury included arterial fibrinoid necrosis, perivascular inflammation (primarily macrophages), and focal infarctions. Vascular lesions were associated with expression of the inflammatory mediators cyclooxygenase 2 (COX-2) and osteopontin in the media of coronary arteries. Myocardial injury, COX-2, and osteopontin expression were markedly attenuated by epl treatment (1 of 10 hearts with damage, P < 0.05 vs. Ang II/salt) and adrenalectomy (2 of 10 hearts with damage, P < 0.05 vs. Ang II/salt). Our data indicate that aldo plays a major role in Ang II-induced vascular inflammation in the heart and implicate COX-2 and osteopontin as potential mediators of the damage.