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Clinical and Experimental Hypertension (1)
Regulatory peptides (1)
The British Journal of Ophthalmology (1)
Zhao, Huawei (3)
Crook, Martin F (1)
DiPette, Donald J. (1)
Flattery, Amy M (1)
Forrest, Gail (1)
Forrest, Michael J (1)
Gupta, Prakash (1)
Katki, Khurshed A. (1)
Mainster, Martin A (1)
Pan, Yi (1)
Roy, Sophie (1)
Ruben, Zadok (1)
Sharif-Rodriguez, Wanda (1)
Supowit, Scott C. (1)
Szeto, Daphne (1)
Urosevic-Price, Olga (1)
Wang, Li (1)
Zhou, Xiaoyan (1)
Zhu, Yonghua (1)
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Bradykinin and Prostaglandin E1 Regulate Calcitonin Gene-Related Peptide Expression in Cultured Rat Sensory Neurons
Supowit, Scott C.
Katki, Khurshed A.
DiPette, Donald J.
Primary cultures of adult rat dorsal root ganglia (DRG) sensory neurons were used to determine whether bradykinin and prostaglandins E1 (PGE1), E2 (PGE2) or I2 (PGI2) stimulate long-term calcitonin gene-related peptide (CGRP) mRNA accumulation and peptide release. Treatment (24 hours) of neurons with either bradykinin or PGE1, significantly increased CGRP mRNA content and iCGRP release. However, PGE2 or PGI2 were without effect. Exposure of the cultured neurons to increasing concentrations of bradykinin or PGE1 demonstrated that the stimulation of CGRP expression was concentration-dependent, while time-course studies showed that maximal levels of CGRP mRNA accumulation and peptide release were maintained for at least 48 hours. Treatment of the neuronal cultures with a bradyknin B2 receptor antagonist significantly inhibited the bradykinin-induced increase in CGRP expression and release. In addition, preincubation of neuronal cultures with the cyclooxygenase inhibitor indomethacin did not alter the PGE1-mediated stimulation of CGRP but blocked completely the bradykinin-induced increase in CGRP production. Therefore, these data indicate that bradykinin and PGE1 can regulate the synthesis and release of CGRP in DRG neurons and that the stimulatory effects of bradykinin on CGRP are mediated by a cyclooxygenase product(s). Thus, these findings suggest a direct relationship between chronic alterations in bradykinin/prostaglandin production that may arise from pathophysiological causes and long-term changes in CGRP expression.
neuropeptides; gene expression; inflammation; pain; sensory nervous system; cell signaling
Chronic Antagonism of the Mineralocorticoid Receptor Ameliorates Hypertension and End Organ Damage in a Rodent Model of Salt-Sensitive Hypertension
Crook, Martin F
Flattery, Amy M
Forrest, Michael J
Clinical and Experimental Hypertension
We investigated the effects of chronic mineralocorticoid receptor blockade with eplerenone on the development and progression of hypertension and end organ damage in Dahl salt-sensitive rats. Eplerenone significantly attenuated the progressive rise in systolic blood pressure (SBP) (204 ± 3 vs. 179±3 mmHg, p < 0.05), reduced proteinuria (605.5 ± 29.6 vs. 479.7 ± 26.1 mg/24h, p < 0.05), improved injury scores of glomeruli, tubules, renal interstitium, and vasculature in Dahl salt-sensitive rats fed a high-salt diet. These results demonstrate that mineralocorticoid receptor antagonism provides target organ protection and attenuates the development of elevated blood pressure (BP) in a model of salt-sensitive hypertension.
mineralocorticoid receptor antagonist; hypertension; end organ protection; eplerenone; Dahl salt-sensitive rats
The effect of chromatic dispersion on pseudophakic optical performance
Mainster, Martin A
The British Journal of Ophthalmology
Monochromatic and chromatic aberrations limit the visual performance of pseudophakic eyes. Chromatic aberration is caused by the chromatic dispersion of optical materials which can be characterised by their Abbe numbers. This study examines how chromatic dispersion affects pseudophakic optical performance at different wavelengths and spatial frequencies.
Abbe numbers were measured for acrylic and silicone intraocular lenses (IOLs). A schematic eye model based on cataract population data was used to compute monochromatic and photopic polychromatic modulation transfer functions (MTFs) for pseudophakic eyes with aspheric IOLs. IOL Abbe numbers were varied without changing other eye model parameters to determine how chromatic dispersion affects pseudophakic MTF and chromatic difference of refraction. Additional calculations were performed for (1) acrylic or silicone materials and (2) high‐pass optical filters blocking either UV radiation or UV radiation and short wavelength visible light.
Shorter wavelengths account for approximately two thirds of pseudophakic chromatic difference of refraction or longitudinal chromatic aberration. Increasing Abbe number (reducing chromatic dispersion) decreases total chromatic difference of refraction and increases photopic polychromatic MTF. For a specific spatial frequency, there is an effective pseudophakic depth of wavelength over which a particular MTF level is achieved or exceeded. Depth of wavelength narrows with decreasing Abbe number or increasing spatial frequency. Blue‐blocking IOL chromophores improve photopic MTF performance by less than 1.5%.
Most pseudophakic longitudinal chromatic aberration arises from the chromatic dispersion of IOLs rather than the cornea and other ocular media. Increasing the Abbe number of optic materials improves overall pseudophakic optical performance. Optical transmission of medium and high spatial frequency modulation information has a spectrum similar to photopic luminous efficiency, accounting for the inability of blue‐blocking chromophores to improve photopic pseudophakic contrast sensitivity significantly and demonstrating the excellent mutual adaptation of modulation transfer by the eye's optics and management of that data by the retina and brain.
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